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.
