A guide to COVID‐19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS‐CoV‐2 infection

Abstract

Antiviral therapies are integral in the fight against SARS‐CoV‐2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID‐19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post‐translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN‐COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post‐translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti‐inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID‐19 infection. In this ‘A Guide To’ article, we provide an in‐depth insight into the development of antiviral therapeutics against SARS‐CoV‐2 and their ability to help fight COVID‐19.

COVID‐19 in early 2023: Structure, replication mechanism, variants of SARS‐CoV‐2, diagnostic tests, and vaccine & drug development studies

“…This drug has been used since December 2021 and has extensive antiviral activity and good off‐target selectivity. 176 , 177 , 178 …”

“…The other antiviral drug is nirmatrelvir/ritonavir (Paxlovid), which inhibits the M pro , 3CL protease, of SARS‐CoV‐2 via reversible covalent bonding between the catalytic cysteine (Cys145) of M pro and the nitrile warhead of nirmatrelvir. This drug has been used since December 2021 and has extensive antiviral activity and good off‐target selectivity 176–178 …”

“…This drug has been used since December 2021 and has extensive antiviral activity and good off-target selectivity. [176][177][178] In order to accelerate the development of antiviral drugs to combat the pandemic, it is essential to predict drug resistance before it becomes prevalent in clinical settings. 179 F I G U R E 4 Virus replication cycle and the steps that are targeted by antiviral drugs.…”

Evaluation of antiviral drugs against newly emerged SARS-CoV-2 Omicron subvariants

“…Remdesivir became the first US Food and Drug Administration (FDA) approved drug in October 2020, and molnupiravir and Nirmatrelvir/ritonavir received emergency use authorisation by the FDA in December 2021 (Brady et al, 2022). Despite these drugs targeting highly conserved regions of the virus genome, genetic mutations could occur in the spike protein and elsewhere in the viral genome .…”

“…Mainly, two classes of targeted antiviral drugs have been developed for treating COVID-19. The first are monoclonal antibodies, which bind directly to the SARS-CoV-2 spike protein and inhibits viral infection (Brady et al, 2022). Although several monoclonal antibodies showed effective virus neutralisation early in the pandemic, they were less or not effective against the emerging Omicron subvariants (Arora et al, 2023).…”