Viral diseases have caused millions of deaths around the world. In the past,
health organizations and pharmaceutical industries have neglected these diseases for
years, mainly because they affected a small geographic population. In contrast, since
2016, several viral outbreaks have been reported worldwide, such as those caused by
Ebola, Zika, and SARS-CoV2 (COVID-19). Thus, these have received more attention,
leading to increased efforts to search for new antiviral drugs. The SARS-CoV-2
pandemic, already responsible for more than 1,254,567 deaths worldwide, is the
greatest example of a virus that has always been present in our society, responsible for
small outbreaks in Asian and Arabic countries in 2004 and 2012. But, investments in
research to identify/discover new drugs and vaccines were only intensified in 2020, in
which only the remdesivir (an FDA-approved drug) was developed to addressCOVID19 until today. Nonetheless, it has been used in hospitals in the United States and
Japan, in emergency cases. Indeed, it justifies greater investments in discovering new
alternatives that could save thousands of people. In this context, improving drug
discovery techniques is fundamental in searching for new therapies that could be
selective and effective to combat SARS-CoV-2. Drug discovery approaches are based
on ligands (Ligand-Based Drug Design - LBDD) or structures (Structure-Based Drug
Discovery - SBDD). Concerning SBDD, it is the main and most evolved technique
used for discovering new drugs. The application of SBDD techniques has improved the
pharmacological arsenal against diverse diseases, which allowed the discovery of
innovative treatments, such as inhibitors of HIV-1 proteases. In this chapter, main
SBDD techniques (i.e. homology modeling; molecular dynamics and docking; de novo
drug discovery; pharmacophore modeling; fragment-based drug discovery; and virtual
high-throughput screenings) applied to discover new hit compounds SARS-CoV-2
(COVID-19) will be discussed in details.
Keywords: Drug discovery, Dynamics simulations, Molecular modeling, SARS-CoV-2, Structure-Based Drug Discovery, TMPRSS2, Virtual screening.
