Synthetic and Herbal Drugs Registered in Clinical Trials on COVID-19: a Review on Recent Research

Abd-Elsalam, S., Esmail, E. S., Khalaf, M., Abdo, E. F., Medhat, M. A., Abd El Ghafar, M. S., ... & Alboraie, M. (2020). Hydroxychloroquine in the treatment of COVID-19: a multicenter randomized controlled study. American Journal of Tropical Medicine and Hygiene, 103(4), 1635-1639. https://doi.org/10.4269%2Fajtmh.20-0873.

Abd‐Elsalam, S., Noor, R. A., Badawi, R., Khalaf, M., Esmail, E. S., Soliman, S., ... & Esmat, G. (2021). Clinical study evaluating the efficacy of ivermectin in COVID‐19 treatment: a randomized controlled study. Journal of Medical Virology, 93(10), 5833-38. https://doi.org/10.1002/jmv.27122.

Ader, F., Bouscambert-Duchamp, M., Hites, M., Peiffer-Smadja, N., Poissy, J., Belhadi, D., ... & Ribeiro, J. M. F. (2022). Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial. The Lancet Infectious Diseases, 22(2), 209-221. https://doi.org/10.1016/S1473-3099(21)004-85-0.

Al-Kuraishy, H. M., Al-Fakhrany, O. M., Elekhnawy, E., Al-Gareeb, A. I., Alorabi, M., De Waard, M., ... & Batiha, G. E. S. (2022). Traditional herbs against COVID-19: back to old weapons to combat the new pandemic. European Journal of Medical Research, 27(1), 186. https://doi.org/10.1186/s40001-022-00818-5.

Angriman, F., Ferreyro, B. L., Burry, L., Fan, E., Ferguson, N. D., Husain, S., ... & Del Sorbo, L. (2021). Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context. The Lancet Respiratory Medicine, 9(6), 655-664. https://doi.org/10.1016/S2213-2600(21)001-39-9.

Arevalo, A. P., Pagotto, R., Pórfido, J., Daghero, H., Segovia, M., Yamasaki, K., … & Crispo, M. (2020). Ivermectin reduces coronavirus infection in vivo: a mouse experimental model. BioRxiv, 11(1), 7132. https://doi.org/10.1101/2020.11.02.363242.

Barrows, N. J., Campos, R. K., Powell, S. T., Prasanth, K. R., Schott-Lerner, G., Soto-Acosta, R., ... & Garcia-Blanco, M. A. (2016). A screen of FDA-approved drugs for inhibitors of Zika virus infection. Cell Host and Microbe, 20(2), 259-270. https://doi.org/10.1016/j.chom.2016.07.004.

Borujerdi, R., Adeli, S. H., Mohammadbeigi, A., Aliasl, F., Asghari, A., Hormati, A., ... & Asghari, M. (2022). Effects of Iranian Polyherbal Syrup (Zufa syrup) on oxygen saturation and clinical symptoms in suspected patients with COVID-19: a triple-blinded, randomized, placebo-controlled trial. Medical Gas Research, 12(2), 44-50. https://doi.org/10.4103/2045-9912.325991.

Brown, M. J., Alazawi, W., & Kanoni, S. (2021). Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. New England Journal of Medicine, 385(12), 1147-1149. https://doi.org/10.1056/nejmc2108482.

Bryant, A., Lawrie, T. A., Dowswell, T., Fordham, E. J., Mitchell, S., Hill, S. R., & Tham, T. C. (2021). Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. American Journal of Therapeutics, 28(4), e434. https://doi.org/10.1097%2FMJT.0000000000001402.

Buonfrate, D., Chesini, F., Martini, D., Roncaglioni, M. C., Fernandez, M. L. O., Alvisi, M. F., ... & Bisoffi, Z. (2022). High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. International Journal of Antimicrobial Agents, 59(2), 106516. https://doi.org/https://doi.org/10.1016/j.ijantimicag.2021.106516.

Calusic, M., Marcec, R., Luksa, L., Jurkovic, I., Kovac, N., Mihaljevic, S., & Likic, R. (2022). Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: an open label, prospective cohort trial with matched controls. British Journal of Clinical Pharmacology, 88(5), 2065-2073. https://doi.org/10.1111/bcp.15126.

Cao, B., Wang, Y., Wen, D., Liu, W., Wang, J., Fan, G., ... & Wang, C. (2020). A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. New England Journal of Medicine, 382(19), 1787-1799. http://doi.org/10.1056/NEJMoa2001282.

Capuano, A., Rossi, F., & Paolisso, G. (2020). Covid-19 kills more men than women: an overview of possible reasons. Frontiers in Cardiovascular Medicine, 7, 131. https://doi.org/10.3389/fcvm.2020.00131.

Cascella, M., Rajnik, M., Aleem, A., Dulebohn, S. C., & Di Napoli, R. (2023). Features, evaluation, and treatment of coronavirus (COVID-19). StatPearls, Treasure Island.

Chen, C., Huang, J., Yin, P., Zhang, Y., Cheng, Z., Wu, J., ... & Wang, X. (2020a). Favipiravir versus arbidol for COVID-19: a randomized clinical trial. MedRxiv, 2020-03. https://doi.org/10.1101/2020.03.17.20037432.

Chen, J., Xia, L., Liu, L., Xu, Q., Ling, Y., Huang, D., ... & Lu, H. (2020b). Antiviral activity and safety of darunavir/cobicistat for the treatment of COVID-19. Open Forum Infectious Diseases, 7(7), ofaa241. https://doi.org/10.1093/ofid/ofaa241.

Ci, X., Li, H., Yu, Q., Zhang, X., Yu, L., Chen, N., ... & Deng, X. (2009). Avermectin exerts anti‐inflammatory effect by downregulating the nuclear transcription factor kappa‐B and mitogen‐activated protein kinase activation pathway. Fundamental and Clinical Charmacology, 23(4), 449-455. https://doi.org/10.1111/j.1472-8206.2009.0-0684.x.

Consortium, W. S. T. (2020). Repurposed antiviral drugs for COVID-19-interim WHO SOLIDARITY trial results. New England Journal of Medicine, 384(6), 497-511. http://doi.org/10.1056/NEJMoa2023184.

Cox, M. J., Loman, N., Bogaert, D., & O'Grady, J. (2020). Co-infections: potentially lethal and unexplored in COVID-19. The Lancet Microbe, 1(1), e11. https://doi.org/10.1016/S2666-5247(20)300-09-4.

Dhawan, M., Parmar, M., Sharun, K., Tiwari, R., Bilal, M., & Dhama, K. (2021). Medicinal and therapeutic potential of withanolides from Withania somnifera against COVID-19. Journal of Applied Pharmaceutical Science, 11(4), 6-13. http://doi.org/10.7324/JAPS.2021.110402.

Di Castelnuovo, A., Costanzo, S., Antinori, A., Berselli, N., Blandi, L., Bonaccio, M., ... & COVID-19 RISK and Treatments (CORIST) Collaboration. (2021). Lopinavir/ritonavir and darunavir/cobicistat in hospitalized COVID-19 patients: findings from the multicenter Italian CORIST study. Frontiers in Medicine, 8, 639970. https://doi.org/10.3389/fmed.2021.639970.

Ding, X. J., Zhang, Y., He, D. C., Zhang, M. Y., Tan, Y. J., Yu, A., ... & Liu, L. (2020). Clinical effect and mechanism of Qingfei Touxie Fuzheng recipe in the treatment of novel coronavirus pneumonia. Herald Med, 39(05), 640-644. 10.3870/j.issn.1004-0781.2020.05.012.

DiNicolantonio, J. J., Barroso-Arranda, J., & McCarty, M. (2020). Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19. Open Heart, 7(2), e001350. http://doi.org/10.1136/openhrt-2020-001350.

Ebina-Shibuya, R., Namkoong, H., Horita, N., Kato, H., Hara, Y., Kobayashi, N., & Kaneko, T. (2021). Hydroxychloroquine and chloroquine for treatment of coronavirus disease 19 (COVID-19): a systematic review and meta-analysis of randomized and non-randomized controlled trials. Journal of Thoracic Disease, 13(1), 202-212. https://doi.org/10.21037%2Fjtd-20-2022.

Echeverría-Esnal, D., Martin-Ontiyuelo, C., Navarrete-Rouco, M. E., De-Antonio Cuscó, M., Ferrández, O., Horcajada, J. P., & Grau, S. (2021). Azithromycin in the treatment of COVID-19: a review. Expert Review of Anti-infective Therapy, 19(2), 147-163. https://doi.org/10.1080/14787210.2020.1813024.

Fallah, A., Razavi Nikoo, H., Abbasi, H., Mohammad-Hasani, A., Hosseinzadeh Colagar, A., & Khosravi, A. (2022). Features of pathobiology and clinical translation of approved treatments for coronavirus disease 2019. Intervirology, 65(3), 119-133. https://doi.org/10.1159/000520234

Fang, J., Li, H., Du, W., Yu, P., Guan, Y. Y., Ma, S. Y., ... & Bian, X. L. (2020). Efficacy of early combination therapy with lianhuaqingwen and arbidol in moderate and severe COVID-19 patients: a retrospective cohort study. Frontiers in Pharmacology, 11, 1465. https://doi.org/10.3389/fphar.2020.560209.

Farooq, S. and Ngaini, Z., (2021). Natural and synthetic drugs as potential treatment for coronavirus disease 2019 (COVID-2019). Chemistry Africa, 4(1), 1-13. https://doi.org/10.1007/s42250-020-00203-x

Fischer, W., Eron Jr, J. J., Holman, W., Cohen, M. S., Fang, L., Szewczyk, L. J., ... & Painter, W. P. (2021). Molnupiravir, an oral antiviral treatment for COVID-19. MedRxiv, 2021.06.17.21258639. https://doi.org/10.1126/scitranslmed.abl7430.

Gautret, P., Lagier, J. C., Honoré, S., Colson, P., & Raoult, D. (2021). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial revisited. International Journal of Antimicrobial Agents, 57(1), 106243. https://doi.org/10.1016%2Fj.ijantimicag.2020.106243.

Giollo, A., Adami, G., Gatti, D., Idolazzi, L., & Rossini, M. (2020). Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID). Annals of the Rheumatic Diseases, 80(2), e12.  https://doi.org/10.1136/annrheumdis-2020-217598.

Group, R. C. (2021). Dexamethasone in hospitalized patients with Covid-19. New England Journal of Medicine, 384(8), 693-704. http://doi.org/10.1056/NEJMoa2021436.

Guimarães, P. O., Quirk, D., Furtado, R. H., Maia, L. N., Saraiva, J. F., Antunes, M. O., ... & Berwanger, O. (2021). Tofacitinib in patients hospitalized with COVID-19 pneumonia. New England Journal of Medicine, 385(5), 406-415. http://doi.org/10.1056/NEJMoa2101643.

Gupta, A., Gonzalez-Rojas, Y., Juarez, E., Crespo Casal, M., Moya, J., Falci, D. R., ... & Shapiro, A. E. (2021). Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab. New England Journal of Medicine, 385(21), 1941-1950. http://doi.org/10.1056/NEJMoa2107934.

Gyselinck, I., Janssens, W., Verhamme, P., & Vos, R. (2021). Rationale for azithromycin in COVID-19: an overview of existing evidence. BMJ Open Respiratory Research, 8(1), e000806. http://doi.org/10.1136/bmjresp-2020-000806.

Hamilton, F. W., Lee, T., Arnold, D. T., Lilford, R., & Hemming, K. (2021). Is convalescent plasma futile in COVID-19? a Bayesian re-analysis of the RECOVERY randomized controlled trial. International Journal of Infectious Diseases, 109, 114-117. https://doi.org/10.1016/j.ijid.2021.06.034.

Hermine, O., Mariette, X., Porcher, R., Resche-Rigon, M., Tharaux, P. L., & Ravaud, P. (2022). Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group. European Respiratory Journal, 60(2). http://doi.org/10.1183/13993003.02523-2021.

Ho, T. Y., Wu, S. L., Chen, J. C., Li, C. C., & Hsiang, C. Y. (2007). Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Research, 74(2), 92-101. https://doi.org/10.1016/j.antiviral.2006.04.014.

Horby, P. W., Mafham, M., Bell, J. L., Linsell, L., Staplin, N., Emberson, J., ... & Landray, M. J. (2020). Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. The Lancet, 396(10259), 1345-52. https://doi.org/10.1016/S0140-6736(20)320-13-4.

Horby, P. W., Mafham, M., Peto, L., Campbell, M., Pessoa-Amorim, G., Spata, E., . . . Hine, P. (2021). Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. MedRxiv, 2021-06. https://doi.org/10.1101/2021.06.15.21258542.

Hu, B., Guo, H., Zhou, P. and Shi, Z.L., (2021). Characteristics of SARS-CoV-2 and COVID-19. Nature Reviews Microbiology, 19(3), 141-154. https://doi.org/10.1038/s41579-020-00459-7 

Humar, A., McGilvray, I., Phillips, M. J., & Levy, G. A. (2004). Severe acute respiratory syndrome and the liver. Hepatology (Baltimore, Md.), 39(2), 291. https://doi.org/10.1002/hep.20069.

Iastrebner, M., Castro, J., Espina, E. G., Lettieri, C., Payaslian, S., Cuesta, M. C., ... & Caruso, V. (2021). Ruxolitinib in severe covid-19 results of a multicenter, prospective, single arm, open-label clinical study to investigate the efficacy and safety of ruxolitinib in patients with covid-19 and severe acute respiratory syndrome. Revista de la Facultad de Ciencias Médicas, 78(3), 294-302. https://doi.org/10.3105310.31053%2F1853.0605.v78.n3.32800

Javorac, D., Grahovac, L., Manić, L., Stojilković, N., Anđelković, M., Bulat, Z., ... & Djordjevic, A. B. (2020). An overview of the safety assessment of medicines currently used in the COVID-19 disease treatment. Food and Chemical Toxicology, 144, 111639. https://doi.org/10.1016/j.fct.2020.111639.

Jeronimo, C. M. P., Farias, M. E. L., Val, F. F. A., Sampaio, V. S., Alexandre, M. A. A., Melo, G. C., ... & Lacerda, M. V. G. (2021). Methylprednisolone as adjunctive therapy for patients hospitalized with coronavirus disease 2019 (COVID-19; Metcovid): a randomized, double-blind, phase IIb, placebo-controlled trial. Clinical Infectious Diseases, 72(9), e373-e381. https://doi.org/10.1093/cid/ciaa1177.

Jiang, Y., Yin, W., & Xu, H. E. (2021). RNA-dependent RNA polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochemical and Biophysical Research Communications, 538, 47-53. https://doi.org/10.1016/j.bbrc.2020.08.116.

Jin, L., Xu, Y., & Yuan, H. (2020). Effects of four types of integrated Chinese and Western medicines for the treatment of COVID-19 in China: a network meta-analysis. Revista da Associação Médica Brasileira, 66, 771-777. https://doi.org/10.1590/1806-9282.66.6.771.

Kageyama, Y., Aida, K., Kawauchi, K., Morimoto, M., Ebisui, T., Akiyama, T., & Nakamura, T. (2022). Jinhua Qinggan granule, a Chinese herbal medicine against COVID‑19, induces rapid changes in the neutrophil/lymphocyte ratio and plasma levels of IL‑6 and IFN‑γ: An open‑label, single‑arm pilot study. World Academy of Sciences Journal, 4(1), 1-8. htts://doi.org/10.3892/wasj.2021.137.

Kalil, A. C., Mehta, A. K., Patterson, T. F., Erdmann, N., Gomez, C. A., Jain, M. K., ... & Colombo, R. E. (2021a). Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-blind, randomised, placebo-controlled, phase 3 trial. The lancet Respiratory Medicine, 9(12), 1365-1376. https://doi.org/10.1016/S2213-2600(21)00384-2.

Kalil, A. C., Patterson, T. F., Mehta, A. K., Tomashek, K. M., Wolfe, C. R., Ghazaryan, V., ... & Beigel, J. H. (2021b). Baricitinib plus remdesivir for hospitalized adults with Covid-19. New England Journal of Medicine, 384(9), 795-807. http://doi.org/10.1056/NEJMoa2031994.

Khan, S., Ali, A., Shi, H., Siddique, R., Nabi, G., Hu, J., ... & Han, G. (2020). COVID-19: Clinical aspects and therapeutics responses. Saudi Pharmaceutical Journal, 28(8), 1004-1008. https://doi.org/10.1016/j.jsps.2020.06.022.

Ko, W. C., Rolain, J. M., Lee, N. Y., Chen, P. L., Huang, C. T., Lee, P. I., & Hsueh, P. R. (2020). Arguments in favour of remdesivir for treating SARS-CoV-2 infections. International Journal of Antimicrobial Agents, 55(4), 105933. https://doi.org/10.1016/j.ijantimicag.2020.105933.

Koshak, A. E., Koshak, E. A., Mobeireek, A. F., Badawi, M. A., Wali, S. O., Malibary, H. M., ... & Madani, T. A. (2021). Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial. Complementary Therapies in Medicine, 61, 102769. https://doi.org/https://doi.org/10.1016/j.ctim.2021.102769.

Laborda, P., Wang, S.-Y., & Voglmeir, J. (2016). Influenza neuraminidase inhibitors: synthetic approaches, derivatives and biological activity. Molecules, 21(11), 1513.https://doi.org/10.3390/molecules21111513.

Lee, T. C., McDonald, E. G., Butler-Laporte, G., Harrison, L. B., Cheng, M. P., & Brophy, J. M. (2021). Remdesivir and systemic corticosteroids for the treatment of COVID-19: a Bayesian re-analysis. International Journal of Infectious Diseases, 104, 671-676. https://doi.org/10.1016/j.ijid.2021.01.065.

Lehrer, S., & Rheinstein, P. H. (2020). Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2. In vivo, 34(5), 3023-3026. https://doi.org/10.21873/invivo.12134.

Lenze, E. J., Mattar, C., Zorumski, C. F., Stevens, A., Schweiger, J., Nicol, G. E., ... & Reiersen, A. M. (2020). Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. The Journal of the American Medical Association, 324(22), 2292-2300. https://doi.org/10.1001/jama.2020.22760.

Li, Z., Chen, H., Zhang, H., Li, Y., Wang, C., Bai, L., ... & Jiang, Z. (2020). Similarity and specificity of traditional Chinese medicine formulas for management of coronavirus disease 2019 and rheumatoid arthritis. ACS Omega, 5(47), 30519-30530. https://doi.org/10.1021/acsomega.0c04377.

Limen, R. Y., Sedono, R., Sugiarto, A., & Hariyanto, T. I. (2022). Janus kinase (JAK)-inhibitors and coronavirus disease 2019 (Covid-19) outcomes: a systematic review and meta-analysis. Expert Review of Anti-Infective Therapy, 20(3), 425-434. https://doi.org/10.1080/14787210.2021.1982695.

Little, P. (2020). Non-steroidal anti-inflammatory drugs and covid-19. British Medical Journal, 368, m1185. https://doi.org/10.1136/bmj.m1185.

Liu, M., Gao, Y., Yuan, Y., Yang, K., Shi, S., Tian, J., & Zhang, J. (2021). Efficacy and safety of herbal medicine (Lianhuaqingwen) for treating COVID-19: a systematic review and meta-analysis. Integrative Medicine Research, 10(1), 100644. https://doi.org/10.1016/j.imr.2020.100644.

Liu, Y., & Breukink, E. (2016). The membrane steps of bacterial cell wall synthesis as antibiotic targets. Antibiotics, 5(3), 28. https://doi.org/10.3390/antibiotics5030028

Liu, Z., Li, X., Gou, C., Li, L., Luo, X., Zhang, C., . . . Li, H. (2020). Effect of Jinhua qinggan granules on novel coronavirus pneumonia in patients. Journal of Traditional Chinese Medicine, 40(3), 467-472. https://doi.org/10.19852/j.cnki.jtcm.2020.03.016.

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., ... & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet, 395(10224), 565-574. https://doi.org/10.1016/S0140-6736(20)30251-8.

Mahase, E. (2021a). Covid-19: Molnupiravir reduces risk of hospital admission or death by 50% in patients at risk, MSD reports. British Medical Journal, 375, n2422. https://doi.org/10.1136/bmj.n2422.

Mahase, E. (2021b). Covid-19: Pfizer’s paxlovid is 89% effective in patients at risk of serious illness, company reports. British Medical Journal, 375, n2713. https://doi.org/10.1136/bmj.n2713.

Mahase, E. (2021c). Covid-19: UK becomes first country to authorise antiviral molnupiravir. In: British Medical Journal, 375: n2697. https://doi.org/10.1136/bmj.n2697.

Mahmoud, D. B., Shitu, Z., & Mostafa, A. (2020). Drug repurposing of nitazoxanide: can it be an effective therapy for COVID-19? Journal of Genetic Engineering and Biotechnology, 18, 1-10. https://doi.org/10.1186%2Fs43141-020-00055-5.

Marconi, V. C., Ramanan, A. V., de Bono, S., Kartman, C. E., Krishnan, V., Liao, R., . . . de Cassia Pellegrini, R. (2021a). Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. The Lancet Respiratory Medicine, 9(12), 1407-1418. https://doi.org/10.1016/S2213-2600(21)00-331-3.

Marconi, V. C., Ramanan, A. V., de Bono, S., Kartman, C. E., Krishnan, V., Liao, R., ... & Zirpe, K. (2021b). Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. The Lancet Respiratory Medicine, 9(12), 1407-1418. https://doi.org/10.1016/s2213-2600(21)003-31-3

Martinez, M. A. (2020). Clinical trials of repurposed antivirals for SARS-CoV-2. Antimicrobial agents and chemotherapy, 64(9), 10-1128. https://doi.org/10.1128/aac.01101-20

Matthay, M. A., & Luetkemeyer, A. F. (2021). IL-6 receptor antagonist therapy for patients hospitalized for COVID-19: who, when, and how? The Journal of the American Medical Association, 326(6), 483-485. https://doi.org/doi:10.1001/jama.2021.11121

Mendieta Zerón, H., Meneses Calderón, J., Paniagua Coria, L., Meneses Figueroa, J., Vargas Contreras, M. J., Vives Aceves, H. L., ... & Anaya Herrera, J. (2021). Nitazoxanide as an early treatment to reduce the intensity of COVID‑19 outbreaks among health personnel. World Academy of Sciences Journal, 3(3), 1-6. https://doi.org/10.3892/wasj.2021.94

Mohan, A., Tiwari, P., Suri, T. M., Mittal, S., Patel, A., Jain, A., . . . Pandey, R. M. (2021). Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial. Journal of Infection and Chemotherapy, 27(12), 1743-1749. https://doi.org/10.1016/j.jiac.2021.08.021.

Mosquera-Sulbaran, J. A., & Hernández-Fonseca, H. (2021). Tetracycline and viruses: a possible treatment for COVID-19? Archives of Virology, 166, 1-7. https://doi.org/10.1007%2Fs00705-020-04860-8

Mostafa, A., Kandeil, A., AMM Elshaier, Y., Kutkat, O., Moatasim, Y., Rashad, A. A., ... & Ali, M. A. (2020). FDA-approved drugs with potent in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2. Pharmaceuticals, 13(12), 443. https://doi.org/10.3390/ph13120443

Muthuri, S. G., Venkatesan, S., Myles, P. R., Leonardi-Bee, J., Al Khuwaitir, T. S., Al Mamun, A., ... & Nguyen-Van-Tam, J. S. (2014). Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. The Lancet Respiratory Medicine, 2(5), 395-404. https://doi.org/10.1016/S2213-2600(14)700-41-4

Nagy-Agren, S. E., & Vasudeva, S. S. (2021). Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infectious Diseases, 22(5), 622-635. https://doi.org/10.1016/S1473-3099(21)007-51-9

Natarajan, S., Anbarasi, C., Sathiyarajeswaran, P., Manickam, P., Geetha, S., Kathiravan, R., ... & Balaji, P. (2020). The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: a structured summary of a study protocol for a randomised controlled trial. Trials, 21(1), 892. https://doi.org/10.1186/s13063-020-04823-z.

National Health Commission & National Administration of Traditional Chinese Medicine. (2020). Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial Version 7). Chinese Medical Journal, 133(09), 1087-1095. https://doi.org/10.1097/CM9.0000000000000819

O’Brien, M. P., Forleo-Neto, E., Musser, B. J., Isa, F., Chan, K. C., Sarkar, N., ... & Weinreich, D. M. (2021). Subcutaneous REGEN-COV antibody combination to prevent Covid-19. New England Journal of Medicine, 385(13), 1184-1195. https://doi.org/10.1056/NEJMoa2109682

Ōmura, S., & Crump, A. (2014). Ivermectin: panacea for resource-poor communities? Trends in Parasitology, 30(9), 445-455. https://doi.org/10.1016/j.pt.2014.07.005

Parums, D. V. (2021). Tocilizumab, a humanized therapeutic IL-6 Receptor (IL-6R) monoclonal antibody, and future combination therapies for severe COVID-19. Medical Science Monitor, 27, e933973-1. https://doi.org/10.12659%2FMSM.933973.

Pindiprolu, S. K. S., & Pindiprolu, S. H. (2020). Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19. Medical Hypotheses, 140, 109765. https://doi.org/10.1016/j.mehy.2020.109765.

Pushpakom, S., Iorio, F., Eyers, P. A., Escott, K. J., Hopper, S., Wells, A., ... & Pirmohamed, M. (2019). Drug repurposing: progress, challenges and recommendations. Nature Reviews Drug Discovery, 18(1), 41-58. https://doi.org/10.1038/nrd.2018.168.

Ranjbar, K., Moghadami, M., Mirahmadizadeh, A., Fallahi, M. J., Khaloo, V., Shahriarirad, R., . . . Gholampoor Saadi, M. H. (2021). Methylprednisolone or dexamethasone, which one is superior corticosteroid in the treatment of hospitalized COVID-19 patients: a triple-blinded randomized controlled trial. BMC Infectious Diseases, 21(1), 1-8. https://doi.org/10.1186/s12879-021-06045-3.

Reis, G., dos Santos Moreira-Silva, E. A., Silva, D. C. M., Thabane, L., Milagres, A. C., Ferreira, T. S., ... & Mills, E. J. (2022). Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the together randomised, platform clinical trial. The Lancet Global Health, 10(1), e42-e51. https://doi.org/10.1016/S2214-109X(21)004-48-4.

Rejinold N, S., Choi, G., Piao, H., & Choy, J. H. (2021). Bovine serum albumin-coated niclosamide-zein nanoparticles as potential injectable medicine against COVID-19. Materials, 14(14), 3792. https://doi.org/10.3390/ma14143792

Rocco, P. R., Silva, P. L., Cruz, F. F., Melo-Junior, M. A. C., Tierno, P. F., Moura, M. A., ... & e Silva, J. R. L. (2021). Early use of nitazoxanide in mild Covid-19 disease: randomised, placebo-controlled trial. European Respiratory Journal, 58(1): 2003725. https://doi.org/10.1183/13993003.03725-2020

Romani, D., Noureddine, O., Issaoui, N., & Brandán, S. A. (2020). Properties and reactivities of niclosamide in different media, a potential antiviral to treatment of COVID-19 by using DFT calculations and molecular docking. Biointerface Research in Applied Chemistry, 10(6), 7295-7328. https://doi.org/10.33263/BRIAC106.72957328.

Rosenberg, E. S., Dufort, E. M., Udo, T., Wilberschied, L. A., Kumar, J., Tesoriero, J., ... & Zucker, H. A. (2020). Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. Journal of the American Medical Association, 323(24), 2493-2502. https://doi.org/10.1001/jama.2020.8630.

Runfeng, L., Yunlong, H., Jicheng, H., Weiqi, P., Qinhai, M., Yongxia, S., ... & Zifeng, Y. (2020). Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacological Research, 156, 104761. https://doi.org/10.1016/j.phrs.2020.104761

Russell, B., Moss, C., Rigg, A., & Van Hemelrijck, M. (2020). COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting? Ecancermedicalscience, 14, 1023. https://doi.org/10.3332%2Fecancer.2020.1023 

Samimi Nemati, A., Tafrihi, M., Sheikhi, F., Rostamian Tabari, A., & Haditabar, A. H. (2020). Designing a new multiepitope-based vaccine against COVID-19. Research in Molecular Medicine, 9(2), 103-118. https://doi.org/10.1155/2020/2683286

Sargiacomo, C., Sotgia, F., & Lisanti, M. P. (2020). COVID-19 and chronological aging: senolytics and other anti-aging drugs for the treatment or prevention of corona virus infection? Aging (Albany NY), 12(8), 6511. https://doi.org/10.18632%2Faging.103001

Scheffers, D. J., & Pinho, M. G. (2005). Bacterial cell wall synthesis: new insights from localization studies. Microbiology and Molecular Biology Reviews, 69(4), 585-607. https://doi.org/10.1128/mmbr.69.4.585-607.2005

Seftel, D., & Boulware, D. R. (2021). Prospective cohort of fluvoxamine for early treatment of coronavirus disease 19. Open Forum Infectious Diseases, 8(2): ofab050. https://doi.org/10.1093/ofid/ofab050.

Sen, I. K., Chakraborty, I., Mandal, A. K., Bhanja, S. K., Patra, S., & Maity, P. (2021). A review on antiviral and immunomodulatory polysaccharides from Indian medicinal plants, which may be beneficial to COVID-19 infected patients. International Journal of Biological Macromolecules, 181, 462-470. https://doi.org/10.1016/j.ijbiomac.2021.03.162

Shen, P., Li, J., Tu, S., Wu, Y., Peng, Y., Chen, G., & Chen, C. (2021). Positive effects of Lianhuaqingwen granules in COVID-19 patients: a retrospective study of 248 cases. Journal of Ethnopharmacology, 278, 114220. https://doi.org/10.1016/j.jep.2021.114220

Shi, N., Liu, B., Liang, N., Ma, Y., Ge, Y., Yi, H., ... & Wang, Y. (2020). Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: a retrospective multicenter cohort study. Pharmacological Research, 161, 105290. https://doi.org/10.1016/j.phrs.2020.105290

Silveira, D., Prieto-Garcia, J. M., Boylan, F., Estrada, O., Fonseca-Bazzo, Y. M., Jamal, C. M., ... & Heinrich, M. (2020). COVID-19: is there evidence for the use of herbal medicines as adjuvant symptomatic therapy? Frontiers in Pharmacology, 11, 1479. https://doi.org/10.3389/fphar.2020.581840.

Sodhi, M., & Etminan, M. (2020). Therapeutic potential for tetracyclines in the treatment of COVID‐19. Pharmacotherapy, 40(5), 487-488. https://doi.org/10.1002%2Fphar.2395.

Kang, S., & Kishimoto, T. (2021). Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Experimental and Molecular Medicine, 53(7), 1116-1123. https://doi.org/10.1038/s12276-021-00649-0.

Tarighi, P., Eftekhari, S., Chizari, M., Sabernavaei, M., Jafari, D., & Mirzabeigi, P. (2021). A review of potential suggested drugs for coronavirus disease (COVID-19) treatment. European Journal of Pharmacology, 895, 173890. https://doi.org/10.1016/j.ejphar.2021.173890

Tay, M. Y. F., Fraser, J. E., Chan, W. K. K., Moreland, N. J., Rathore, A. P., Wang, C., ... & Jans, D. A. (2013). Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Research, 99(3), 301-306. https://doi.org/10.1016/j.antiviral.2013.06.002

Tian, J., Yan, S., Wang, H., Zhang, Y., Zheng, Y., Wu, H., ... & Tong, X. (2020). Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study. Pharmacological Research, 161, 105127. https://doi.org/10.1016/j.phrs.2020.105127

Vecchié, A., Batticciotto, A., Tangianu, F., Bonaventura, A., Pennella, B., Abenante, A., ... & Dentali, F. (2021). High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study. Internal and Emergency Medicine, 16(7), 1913-1919. https://doi.org/10.1007/s11739-021-02800-1

Venditto, V. J., Haydar, D., Abdel-Latif, A., Gensel, J. C., Anstead, M. I., Pitts, M. G., ... & Feola, D. J. (2021). Immunomodulatory effects of azithromycin revisited: potential applications to COVID-19. Frontiers in Immunology, 12, 574425. https://doi.org/10.3389/fimmu.2021.574425

Wagstaff, K. M., Sivakumaran, H., Heaton, S. M., Harrich, D., & Jans, D. A. (2012). Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochemical Journal, 443(3), 851-856. https://doi.org/10.1042/BJ20120150

Wang, H., Xu, B., Zhang, Y., Duan, Y., Gao, R., He, H., ... & Li, J. (2021). Efficacy and safety of traditional Chinese medicine in coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Frontiers in Pharmacology, 12, 609213. https://doi.org/10.3389/fphar.2021.609213

Wang, J. (2020). Fast identification of possible drug treatment of coronavirus disease-19 (COVID-19) through computational drug repurposing study. Journal of Chemical Information and Modeling, 60(6), 3277-3286. https://doi.org/10.1021/acs.jcim.0c00179

Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., ... & Yancopoulos, G. D. (2021). REGEN-COV antibody combination and outcomes in outpatients with Covid-19. New England Journal of Medicine, 385(23), e81. https://doi.org/10.1056/nejmoa2108163

Wen, W., Chen, C., Tang, J., Wang, C., Zhou, M., Cheng, Y., ... & Mao, Q. (2022). Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19： a meta-analysis. Annals of Medicine, 54(1), 516-523. https://doi.org/10.1080/07853890.2022.2034936

World Health Organization. (2022). Weekly epidemiological update on COVID-19. (Ed 144). [25 May 2022]. Retrieved from https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---25-may-2022

Wu, R., Wang, L., Kuo, H. C. D., Shannar, A., Peter, R., Chou, P. J., ... & Kong, A. N. (2020). An update on current therapeutic drugs treating COVID-19. Current Pharmacology Reports, 6(3), 56-70. https://doi.org/10.1007/s40495-020-00216-7

Xiong, W. Z., Wang, G., Du, J., & Ai, W. (2020). Efficacy of herbal medicine (Xuanfei Baidu decoction) combined with conventional drug in treating COVID-19: a pilot randomized clinical trial. Integrative Medicine Research, 9(3), 100489. https://doi.org/10.1016/j.imr.2020.100489.

Xu, X., Han, M., Li, T., Sun, W., Wang, D., Fu, B., ... & Wei, H. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proceedings of the National Academy of Sciences, 117(20), 10970-10975. https://doi.org/10.1073/pnas.2005615117.

Yadav, R., Hasan, S., Mahato, S., Celik, I., Mary, Y. S., Kumar, A., ... & Chaudhary, J. K. (2021). Molecular docking, DFT analysis, and dynamics simulation of natural bioactive compounds targeting ACE2 and TMPRSS2 dual binding sites of spike protein of SARS CoV-2. Journal of Molecular Liquids, 342, 116942. https://doi.org/10.1016/j.molliq.2021.116942

Yang, S. N., Atkinson, S. C., Wang, C., Lee, A., Bogoyevitch, M. A., Borg, N. A., & Jans, D. A. (2020). The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Research, 177, 104760. https://doi.org/10.1016/j.antiviral.2020.104760.

Yin, W., Mao, C., Luan, X., Shen, D. D., Shen, Q., Su, H., ... & Xu, H. E. (2020). Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science, 368(6498), 1499-1504. https://doi.org/10.1126/science.abc1560.

Yu, S., Piao, H., Rejinold, N. S., Jin, G., Choi, G., & Choy, J. H. (2021). Niclosamide-clay intercalate coated with nonionic polymer for enhanced bioavailability toward covid-19 treatment. Polymers, 13(7), 1044. https://doi.org/10.3390/polym13071044.

Zakeri, B., & Wright, G. D. (2008). Chemical biology of tetracycline antibiotics. Biochemistry and Cell Biology, 86(2), 124-136. https://doi.org/10.1139/o08-002.

Zhang, X., Song, Y., Ci, X., An, N., Ju, Y., Li, H., ... & Deng, X. (2008). Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice. Inflammation Research, 57(11), 524-529. https://doi.org/10.1007/s00011-008-8007-8.

Zhang, X., Xue, Y., Chen, X., Wu, J. M., Su, Z. J., Sun, M., ... & Chen, Q. (2021). Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19: a retrospective cohort study. Journal of Integrative Medicine, 19(1), 36-41. https://doi.org/10.1016/j.joim.2020.10.002.

Zhang, Y., Yao, Y., Yang, Y., & Wu, H. (2021). Investigation of anti-SARS, MERS, and COVID-19 effect of Jinhua Qinggan granules based on a network pharmacology and molecular docking approach. Natural Product Communications, 16(5), 1934578X211020619. https://doi.org/10.1177/1934578X211020619.

Zou, L., Dai, L., Zhang, X., Zhang, Z., & Zhang, Z. (2020). Hydroxychloroquine and chloroquine: a potential and controversial treatment for COVID-19. Archives of Pharmacal Research, 43, 765-772. https://doi.org/10.1007/s12272-020-01258-7.

Zumla, A., Chan, J. F., Azhar, E. I., Hui, D. S., & Yuen, K. Y. (2016). Coronaviruses-drug discovery and therapeutic options. Nature Reviews Drug Discovery, 15(5), 327-347. https://doi.org/10.1038/nrd.2015.37