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Review
. 2023 Dec 2:6:100208.
doi: 10.1016/j.crmicr.2023.100208. eCollection 2024.

Clinical development of antivirals against SARS-CoV-2 and its variants

Qiaoshuai Lan  1   2 , Yan Yan  1 , Guangxu Zhang  1 , Shuai Xia  1 , Jie Zhou  2   3   4 , Lu Lu  1 , Shibo Jiang  1
Affiliations
Review

Clinical development of antivirals against SARS-CoV-2 and its variants

Qiaoshuai Lan et al. Curr Res Microb Sci. .

Abstract

The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although many newly developed antivirals and repurposed antivirals have been applied to the treatment of coronavirus disease 2019 (COVID-19), antivirals showing satisfactory clinical efficacy are few in number. In addition, the loss of sensitivity to variants of concern (VOCs) and lack of oral bioavailability have also limited the clinical application of some antivirals. These facts remind us to develop more potent and broad-spectrum antivirals with better pharmacokinetic/pharmacodynamic properties to fight against infections from SARS-CoV-2, its variants, and other human coronaviruses (HCoVs). In this review, we summarize the latest advancements in the clinical development of antivirals against infections by SARS-CoV-2 and its variants.

Keywords: Antivirals; COVID-19; Host factor; SARS-CoV-2; Variants; Viral factor.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
The life cycle of SARS-CoV-2 and targets for some antivirals. Entry-stage: SARS-CoV-2 particles use their Spike (S) protein to interact with receptor molecules (human ACE2) for viral entry. During the viral entry process, monoclonal antibodies can inhibit the interaction of S protein and ACE2 protein to inhibit viral entry, while TMPRSS-2 inhibitors and Cathepsin B/L inhibitors can inhibit proteolytic activation of spike protein to inhibit viral entry. Peptide inhibitors targeting HR1 (EK1 and HR2P) can inhibit 6-HB formation to block viral entry. Post-entry stage: Viral protein cleavage and RNA synthesis are important processes for the SARS-CoV-2 replication cycle. Mpro and PLpro are important proteases responsible for viral protein cleavage, and these processes can be halted by protease inhibitors, for example, nirmatrelvir (PF-07321332) and ensitrelvir. RdRp is important for viral RNA synthesis, and these processes can be stopped by RdRp inhibitors, such as remdesivir, VV116, and molnupiravir.
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