Recent advances in developing small-molecule inhibitors against SARS-CoV-2

Abstract

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

A Palmitic Acid-Conjugated, Peptide-Based pan-CoV Fusion Inhibitor Potently Inhibits Infection of SARS-CoV-2 Omicron and Other Variants of Concern

“…The outbreak of COVID-19 sparked the development of a broad spectrum of antivirals, including therapeutic monoclonal antibodies, protein-, peptide- and small-molecule compound-based inhibitors, against SARS-CoV-2 infection [ 12 , 30 , 31 ]. However, the newly emerged SARS-CoV-2 VOCs, such as Omicron, have shown increasing resistance to some developed antiviral treatments and, even more concerning, SARS-CoV-2 RBD-specific neutralizing antibodies and vaccines being used worldwide [ 6 , 32 , 33 , 34 , 35 ].…”

Validation and invalidation of SARS-CoV-2 main protease inhibitors using the Flip-GFP and Protease-Glo luciferase assays

“…For these reasons, M pro becomes a high-profile drug target for the development of broad-spectrum antivirals. Structurally disparate compounds including FDA-approved drugs and bioactive compounds have been reported as M pro inhibitors 6 , 7 , 8 , 9 , 10 , several of which also have in vivo antiviral efficacy against SARS-CoV-2 11 , 12 , 13 , 14 , 15 .…”

A Drug Repurposing Approach for Antimalarials Interfering with SARS-CoV-2 Spike Protein Receptor Binding Domain (RBD) and Human Angiotensin-Converting Enzyme 2 (ACE2)

“…The S1 subunit contains a receptor-binding domain (RBD), which directly mediates this binding, and an N-terminal domain, the same motif that is also present for SARS-CoV-2 [8]. The identification of small molecule inhibitors targeting these viral proteins, host proteins or RNA assemblies unique to SARS-CoV-2 are thus required [9,10]. In this connection, several of these targets are under examination [11][12][13].…”

“…In this connection, several of these targets are under examination [11][12][13]. The screening of drugs approved by the FDA for other purposes is an attractive strategy [14], as this has the potential of providing expedited treatment of SARS-CoV-2 infection [9,15,16]. Specifically, targeting the ACE2-RBD assembly with low molecular weight drugs [17,18] and identifying other small molecules interfering with this recognition mechanism will prevent cell invasion by the virus, and thereby block infection [19].…”