Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2

Author(s): Sounik Manna, Trinath Chowdhury, Piyush Baindara, Santi M. Mandal*

Journal Name: Current Protein & Peptide Science

Volume 21 , Issue 10 , 2020


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Abstract:

Infectious diseases caused by viruses have become a serious public health issue in the recent past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion proteins play an important role in the fusion process and in infection establishment. Because of this, the fusion process targeting antivirals become an interest to fight against viral diseases caused by the enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat the viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide. There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = - 62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed libraries may help to block the target sites competitively to successfully control COVID-19.

Keywords: Viral infections, enveloped viruses, fusion protein, antiviral peptides, FBDD, SARS-CoV-2.

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VOLUME: 21
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Year: 2020
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DOI: 10.2174/1389203721666200908164641
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