Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein
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Cellular and Molecular Bioengineering (Ó 2020) https://doi.org/10.1007/s12195-020-00658-5
Original Article
Structure-Based Design of Novel Peptidomimetics Targeting the SARS-CoV-2 Spike Protein MANIKANDAN ALAGUMUTHU, SAJJAN RAJPOOT, and MIRZA S. BAIG Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, MP 453552, India (Received 27 June 2020; accepted 26 September 2020) Associate Editor Michael R. King oversaw the review of this article.
Abstract Purpose—SARS-CoV-2 is a SARS-like novel coronavirus strain first identified in December 2019 in Wuhan, China. The virus has since spread globally, resulting in the current ongoing coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 spike protein is a critical factor in the COVID-19 pathogenesis via interactions with the host cell angiotensin-converting enzyme 2 (ACE2) PD domain. Worldwide, numerous efforts are being made to combat COVID19. In the current study, we identified potential peptidomimetics against the SARS-CoV-2 spike protein. Methods—We utilized the information from ACE2-SARSCoV-2 binary interactions, and based on crucial interacting interface residues, novel peptidomimetics were designed. Results—Top scoring peptidomimetics were found to bind at the ACE2 binding site of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Conclusions—The current studies could pave the way for further investigations of these novel and potent compounds against the SARS-CoV-2. Keywords—COVID-19, SARS-CoV-2 spike protein, Virtual screening, Molecular docking, Peptidomimetic.
INTRODUCTION Coronaviruses are a group of RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is also caused by certain
Address correspondence to Mirza S. Baig, Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Indore, MP 453552, India. Electronic mail: [email protected] Manikandan Alagumuthu and Sajjan Rajpoot have contributed equally to this work.
other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID19.1 COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a case-fatality rate of 2:3%, with higher rates among elderly patients and patients with concurrent medical conditions (WHO, May.31 During attachment and penetration, the SARS-CoV-2 attaches itself to a host cell ACE2 PD domain through its spike (S) protein (Li et al.15,18 Structurally, the coronavirus has the most massive known RNA genome of 26 to 32 kb amongst other known viruses, characterized by non-segmented, positive-sense single-stranded RNA.6 This genome encodes for four major structural proteins of the virus, including; Nucleocapsid (N), Envelope (E), Membrane (M), and Spike (S) proteins (Li et al.15,18 The membrane and envelope proteins are associated with virus assem
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