Antiviral drugsThere is no globally recognised antiviral drug that is effective for treatment. Remdensivir and molnupiravir show moderate efficacy. Antiviral drugs are hard to find because of the diversity and cell-parasitic nature of viruses.
It has taken a long time to find effective drugs for HIV or hepatitis C. The challenge is to find a therapeutic dose window between the side effects of antiviral drugs and their effect against the viral disease.
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External resource |
ANTIVIRAL DRUGS This table displays the main drugs investigated
| Compound | Class | Ref | Status for Covid-19 | Notes |
|---|---|---|---|---|
Paxlovid (Nirmatrelvir Ritonavir
 )
|
Protease inhibitor/CYP3A inhibitor (respectively) | 
|
Approved.
Effective in clinical trials
| -Oral SARS-CoV-2 M pro inhibitor. Nirmatrelvir is responsible for the antiviral activity of the medication while ritonavir is stabilizing its action by inhibiting CYP3A4, the cellular enzyme that metabolizes Nirmatrelvir.
|
|
Remdesivir
|
Viral polymerase inhibitor |
| Approved.
Weakly effective in clinical trials
| - |
|
Molnupiravir (MK-4482 or EIDD-2801)
|
Viral polymerase inhibitor |
|
Approved . Weakly effective in clinical trials
| -Repurposed: Nucleotide analog designed against Influenza. |
| Bemnifosbuvir (AT-527) | Viral polymerase inhibitor |
| Under investigation | - Nucleotide analog that inhibits viral polymerase at two regions. |
|
Fluvoxamine
|
Unknown |
|
Rejected for COVID-19 treatment.
| -Repurposed: antidepressant of the selective serotonin reuptake inhibitor (SSRI) class |
|
Invermectin
|
Unknown |
|
No evidence of SARS-CoV-2 inactivation
| -Repurposed: Inhibits glutamate-gated chloride channels common to invertebrate nerve and muscle cells. |
|
Favipiravir
|
Viral polymerase inhibitor |
|
No evidence of SARS-CoV-2 inactivation | -Repurposed |
| Ritonavir
,
Lopinavir
|
Protease inhibitor |
|
No-benefit in clinical trials
| -Repurposed: Molecules targeting HIV protease which is a ASP protease, but SARS-Cov proteases are THIOL proteases. |
|
Darunavir
|
Protease inhibitor |
| No evidence of SARS-CoV-2 inactivation | -Repurposed |
| Camostat
|
Spike maturation inhibitor |
|
| -TMPRSS2 inhibitor that may prevent Spike cleavage and activation. Spike could still be activated by cathepsin or furin
|
|
Hydroxychloroquine
|
Endosome fusion inhibitor |
|
No-benefit in clinical trials
| -Repurposed: Non-specific anti-malaria drug. May prevent virus entry by modifying endosomal pH. |
|
Umifenovir/Arbidol
|
Endosome fusion inhibitor |
|
No-benefit in clinical trials
| -Repurposed: Anti influenza drug |
Camostat mesilate therapy for COVID-19.
Uno Y.
Intern Emerg Med. 2020 Apr 29.
The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade.
Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E.
Antiviral Res. 2020 Apr;176:104742
Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E.
Antiviral Res. 2020 Apr;176:104742
An exploratory randomized controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI)
Yueping Li, Zhiwei Xie, Weiyin Lin, Weiping Cai, Chunyan Wen, Yujuan Guan, Xiaoneng Mo, Jian Wang, Yaping Wang, Ping Peng, Xudan Chen, Wenxin Hong, Guangming Xiao, Jinxin Liu, Lieguang Zhang, Fengyu Hu, Feng Li, Feng Li, Fuchun Zhang, Xilong Deng, Linghua Li
medXriv
Hydroxychloroquine in the treatment and prophylaxis of SARS-CoV-2 infection in non-human primates
Pauline Maisonnasse, J?r?mie Guedj, Vanessa Contreras, Sylvie Behillil, Caroline Solas, Romain Marlin, Thibaut Naninck, Andres Pizzorno, Julien Lemaitre, Antonio Gon?alves, Nidhal Kahlaoui, Olivier Terrier, Raphael Ho Tsong Fan, Vincent Enouf, Nathalie Dereuddre- Bosquet, Angela Brisebarre, Franck Toure, Catherine Chapon, Bruno Hoen, Bruno Lina, Manuel Rosa Calatrava, Sylvie van der Werf, Xavier de Lamballerie, Roger Le Grand
Preprint, nature
A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C.
N Engl J Med. 2020 May 7;382(19):1787-1799.
NIH clinical trial shows Remdesivir accelerates recovery from advanced COVID-19
Preliminary results
Molnupiravir: coding for catastrophe
Brandon Malone & Elizabeth A. Campbell
Nature Structural & Molecular Biology volume 28, pages706?708 (2021)
Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial
Yeming Wang, MD ?
Dingyu Zhang, MD ?
Prof Guanhua Du, PhD ?
Prof Ronghui Du, MD ?
Prof Jianping Zhao, MD ?
Prof Yang Jin, MD ?
Prof Shouzhi Fu, MD ?
Prof Ling Gao, MD ?
Prof Zhenshun Cheng, MD ?
Prof Qiaofa Lu, MD ?
Prof Yi Hu, MD ?
Prof Guangwei Luo, MD ?
Prof Ke Wang, PhD
Prof Yang Lu, PhD
Huadong Li, MD
Shuzhen Wang, MS
Shunan Ruan, MS
Chengqing Yang, MD
Chunlin Mei, MD
Yi Wang, MD
Dan Ding, MD
Feng Wu, MD
Xin Tang, MD
Xianzhi Ye, MD
Yingchun Ye, MD
Bing Liu, MD
Jie Yang, MD
Wen Yin, MD
Aili Wang, MD
Guohui Fan, MS
Fei Zhou, MD
Zhibo Liu, MD
Xiaoying Gu, PhD
Jiuyang Xu, MD
Lianhan Shang, MD
Yi Zhang, MD
Lianjun Cao, BD
Tingting Guo, BD
Yan Wan, BD
Hong Qin, PhD
Yushen Jiang, PhD
Prof Thomas Jaki, PhD
Prof Frederick G Hayden, MD
Prof Peter W Horby, MD
Prof Bin Cao, MD
Prof Chen Wang, MD
Lancet, April 29, 2020
Remdesivir for the Treatment of Covid-19 - Preliminary Report
Beigel JH, Tomashek KM, Dodd LE, et al.
N Engl J Med. 2020
Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets
Robert M. Cox, Josef D. Wolf & Richard K. Plemper
Nature Microbiology volume 6, pages11?18 (2021)
An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19
Dafydd R Owen et al.
Science. 2021 Nov 2
Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial
Dafydd Eric J Lenze et al.
JAMA. 2020 Dec 8; 324(22): 2292?2300.
A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase
Ashleigh Shannon, V?ronique Fattorini, Bhawna Sama, Barbara Selisko, Mikael Feracci, Camille Falcou, Pierre Gauffre, Priscila El Kazzi, Adrien Delpal, Etienne Decroly, Karine Alvarez, C?cilia Eydoux, Jean-Claude Guillemot, Adel Moussa, Steven S. Good, Paolo La Colla, Kai Lin, Jean-Pierre Sommadossi, Yingxiao Zhu, Xiaodong Yan, Hui Shi, Fran?ois Ferron & Bruno Canard
Nature Communications volume 13, Article number: 621 (2022)
PANORAMIC Trial Collaborative Group
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial
Lancet, December 22, 2022
Ronza Najjar-Debbiny, Naomi Gronich, Gabriel Weber, Johad Khoury, Maisam Amar, Nili Stein, Lee Hilary Goldstein, Walid Saliba
Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients
Clin Infect Dis. 2022 Jun 2
FDA Food and drugs administration.
Memorandum Explaining Basis for Declining Request for Emergency
Use Authorization of Fluvoxamine Maleate
2022