Coronavirus disease-19, caused by the novel β-coronavirus SARS-CoV-2, has created a global pandemic unseen in a century. Rapid worldwide efforts have enabled the characterization of the virus and its pathogenic mechanism. An early key finding is that SARS-CoV-2 uses spike proteins, the virus' most exposed structures, to bind to human ACE2 receptors and initiate cell invasion. Competitive targeting of the spike protein is a promising strategy to neutralize virus infectivity. This review article summarizes the discovery, binding modes and eventual applications of several classes of (bio)molecules targeting the spike protein: antibodies, nanobodies, soluble ACE2 variants, miniproteins, peptides and small molecules.
WHO has declared COVID-19 a pandemic, which has affected the whole world and has caused unprecedented social and economic disruption. Since the emergence of the disease, several druggable targets have been suggested including 3-chymotrypsin-like protease (3CLpro), spike, RNA-dependent RNA polymerase (RdRp), and the papain-like protease (PLpro) computational approach. From the beginning, viral replication has been the main focus for any antiviral drug development for viral diseases, including HCV, influenza virus, zika virus, norovirus, measles, dengue virus, and coronaviruses. This review lists the nucleoside, nucleotide, and non-nucleoside RdRp inhibitor analogues of various viral diseases that may be evaluated for drug development to treat COVID-19.
The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy De novo drug discovery takes years to move from idea and/or pre-clinic to market, and it is not a short-term solution for the current SARS-CoV-2 pandemic Drug repurposing is perhaps the only short-term solution, while vaccination is a middle-term solution Here, we describe the discovery path of the HCV NS3–4A protease inhibitors boceprevir and telaprevir as SARS-CoV-2 main protease (3CLpro) inhibitors Based on our hypothesis that α-ketoamide drugs can covalently bind to the active site cysteine of the SARS-CoV-2 3CLpro, we performed docking studies, enzyme inhibition and co-crystal structure analyses and finally established that boceprevir, but not telaprevir, inhibits replication of SARS-CoV-2 and mouse hepatitis virus (MHV), another coronavirus, in cell culture Based on our studies, the HCV drug boceprevir deserves further attention as a repurposed drug for COVID-19 and potentially other coronaviral infections as well
In December 2019, an infectious disease was detected in Wuhan, China, caused by a new pathogenic coronavirus, named SARS-CoV-2 It spread very rapidly, and on March 11th of 2020, the outbreak was declared a pandemic by the World Health Organization Currently, effective treatment options remain limited SARS-CoV-2 enzyme main protease (MPRO) plays a pivotal role in the viral life cycle, making it a putative drug target In order to identify suitable hits to develop inhibitors with adequate antiviral properties, we explored the LASSBio Chemical Library employing multiple strategies of virtual screening A fragment-based pharmacophore model enabled the identification of key interactions involved in the molecular recognition at the catalytic site of MPRO, namely, with amino acid residues His41, His163 and Glu166 Docking-based virtual screening was performed, leading to the identification of LASSBio-1945 (9), a new hit of MPRO, presenting an IC50 = 15 97 μM This compound, an 1,3-benzodioxolyl sulfonamide, represents an interesting starting point for subsequent hit-to-lead optimization steps and, to the best of our knowledge, a new distinct chemotype for MPRO inhibition
New tridecaptin analogues are cheaper to make and retain strong Gram-negative activity.
