Advanced search
Start date
Betweenand

On the development of SARS-CoV-2 3CL Mpro Coronavirus main protease inhibitors as antiviral agents

Abstract

Despite the FDA approval of Paxlovid and Molnupiravir and the hope that they will act on the omicron strain - both are effective on the delta strain; there is still room for nirmatrelvir optimization. Considering the excellent results obtained through the FAPESP project #2020/04653-2, we will continue the in vitro and in vivo assays of the best-identified antivirals (Neq1119, Neq1167, Neq1184) for the establishment of in vivo proof of concept (PoC) with desire for better efficacy and tolerability. While there is clear evidence of antiviral action in the new variants of SARS-CoV-2, its main protease Mpro continues to experiment with mutations that need to be constantly challenged. Of particular interest are positions P3 and P4 of the peptide-like inhibitors, for improvement to get higher affinity Mpro inhibitors can be envisaged. In addition, P2 is also amenable to optimization, and we will investigate new unnatural prolines and new six-membered rings. Too, we will endeavor to evaluate new warheads with differing electrophilicity character. Thus, this project will apply hypothesis-driven molecular design to synthesize and structurally characterize new chemical entities as inhibitors of SARS-CoV-2 Mpro with antiviral action in vitro and in vivo. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list by writing to: cdi@fapesp.br.