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Review
. 2024 Jan 30;3(1):100144.
doi: 10.1016/j.cellin.2023.100144. eCollection 2024 Feb.

Development of SARS-CoV-2 entry antivirals

Meiyue Dong  1 , Jazmin M Galvan Achi  2 , Ruikun Du  1   3 , Lijun Rong  2 , Qinghua Cui  1   3
Affiliations
Review

Development of SARS-CoV-2 entry antivirals

Meiyue Dong et al. Cell Insight. .

Abstract

The global outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatened human health and public safety. The development of anti-SARS-CoV-2 therapies have been essential to curb the spread of SARS-CoV-2. Particularly, antivirals targeting viral entry have become an attractive target for the development of anti-SARS-CoV-2 therapies. In this review, we elucidate the mechanism of SARS-CoV-2 viral entry and summarize the development of antiviral inhibitors targeting viral entry. Moreover, we speculate upon future directions toward more potent inhibitors of SARS-CoV-2 entry. This study is expected to provide novel insights for the efficient discovery of promising candidate drugs against the entry of SARS-CoV-2, and contribute to the development of broad-spectrum anti-coronavirus drugs.

Keywords: Antiviral inhibitors; Cell entry; SARS-CoV-2; SARS-CoV-2 variants.

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Conflict of interest statement

After deliberative consultation and discussion, the authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Characteristics of SARS-CoV-2 Spike (S) protein. (A) Schematic representation of structure of SARS-CoV-2 virions. (B) Schematic drawing of the 1D structure of SARS-CoV-2 spike. FP (fusion peptide), HR1 (heptad repeat 1), and HR2 (heptad repeat 2) are structural units in coronavirus S2 that function in membrane fusion. SP, signal peptide; TM, transmembrane anchor; CP, cytoplasmic tail; S1/S2, cleavage site at S1/S2 boundary; S2’, a second cleavage site within S2.
Fig. 2
Fig. 2
SARS-CoV-2 replication cycle and promising drugs or small molecule compounds to inhibit viral infection. Upon binding to host receptor ACE2, the SARS-CoV-2 S protein can be activated by TMPRSS2 cleavage at the cell surface, resulting in fusion with plasma membrane (A). Alternatively, the virions enter cells via clathrin-dependent endocytosis, and the fusion process can be primed by endosomal cathepsin L (B).
Fig. 3
Fig. 3
Drug discovery strategies to target SARS-CoV-2 entry.
See this image and copyright information in PMC

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