Peptidomimetic and Peptide-Derived Against 3CLpro from Coronaviruses

 SARS-CoV-2 is an RNA virus responsible for causing pandemic COVID-19, which has taken on unprecedented proportions so far in global health and economic aspects. In this context, the search for effective drugs against SARS-CoV-2 has become a priority for the global scientific community, where the chymotrypsin-like picornavirus 3C-like protease (3CLpro, which is also named as main protease (Mpro), or only 3C) is a promising druggable target since it is crucial for the process of viral replication. Several 3CLpro inhibitors have been recently reported in the literature. Thus, peptidomimetics have emerged as a potential class for designing new effective drugs against COVID-19, in addition to lopinavir/ritonavir, in which these drugs are currently being investigated in clinical trials. In this chapter, we describe peptidomimetic and peptide-derived inhibitors of 3CLpro from SARS-CoV-2, and also SARS- and MERSCoV viruses, summarizing all relevant studies based on warhead groups utilization and SAR analysis for all of them in order to contribute to the development of compounds more selective, effective, and low-costs to combat these emerging viruses

Keywords: 3CLpro inhibitors, Drug Design, MERS-CoV, Peptidomimetics, SARS-CoV, SARS-CoV-2.