Small molecules in the treatment of COVID-19

Abstract

The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.

Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines

“…Currently, many broad-spectrum compounds (e.g., Remdesivir, Molnupiravir, VV116, and Azvudine) have already been approved for the treatment of COVID-19 by targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). 103 – 105 In addition, several candidate compounds are undergoing clinical trials that could enrich anti-COVID-19 drugs. 105 Moreover, small-molecule compounds reportedly protect against SARS-CoV-2 infection by blocking the HR1-HR2 bundle assembly, paving a potential way for screening and designing broad-spectrum antiviral inhibitors.…”

“… 103 – 105 In addition, several candidate compounds are undergoing clinical trials that could enrich anti-COVID-19 drugs. 105 Moreover, small-molecule compounds reportedly protect against SARS-CoV-2 infection by blocking the HR1-HR2 bundle assembly, paving a potential way for screening and designing broad-spectrum antiviral inhibitors.…”

Hematological Questions in Personalized Management of COVID-19 Vaccination

“…To date, several effective treatments against COVID-19 have been explored, including dexamethasone, monoclonal antibodies (tocilizumab), and other small molecules targeting specific signals and functions. Small molecules such as remdesivir, paxlovid, and baricitinib have already been approved in many countries [ 3 , 4 ]. Vaccination is an effective strategy to control the pandemic.…”

Design of hACE2-based small peptide inhibitors against spike protein of SARS-CoV-2: a computational approach

“…The proposed peptide, however, was unable to preserve secondary structure, making it unable to completely block the SARS-CoV binding surface. Cyclodextrins and broad-spectrum antiviral nanoparticles were developed, simulated, and used to prevent additional viruses [ 21 – 24 ]. They are category 2 or 3 inhibitors, although it is unclear if they will work against SARS-CoV-2.…”