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Computational and in vitro experimental analyses of the anti-COVID-19 potential of Mortaparib and MortaparibPlus.
Kumar, Vipul; Sari, Anissa Nofita; Meidinna, Hazna Noor; Dhanjal, Jaspreet Kaur; Subramani, Chandru; Basu, Brohmomoy; Kaul, Sunil C; Vrati, Sudhanshu; Sundar, Durai; Wadhwa, Renu.
  • Kumar V; DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India.
  • Sari AN; AIST-India DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 3058565, Japan.
  • Meidinna HN; AIST-India DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 3058565, Japan.
  • Dhanjal JK; AIST-India DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 3058565, Japan.
  • Subramani C; Department of Computational Biology, Indraprastha Institute of Information Technology Delhi, Okhla Industrial Estate, Phase III, New Delhi 110020, India.
  • Basu B; Regional Centre for Biotechnology (RCB), Faridabad 121001, India.
  • Kaul SC; Regional Centre for Biotechnology (RCB), Faridabad 121001, India.
  • Vrati S; AIST-India DAILAB, DBT-AIST International Center for Translational and Environmental Research (DAICENTER), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 3058565, Japan.
  • Sundar D; Regional Centre for Biotechnology (RCB), Faridabad 121001, India.
  • Wadhwa R; DAILAB, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India.
Biosci Rep ; 41(10)2021 10 29.
Article in English | MEDLINE | ID: covidwho-1510636
ABSTRACT
Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has become a global health emergency. Although new vaccines have been generated and being implicated, discovery and application of novel preventive and control measures are warranted. We aimed to identify compounds that may possess the potential to either block the entry of virus to host cells or attenuate its replication upon infection. Using host cell surface receptor expression (angiotensin-converting enzyme 2 (ACE2) and Transmembrane protease serine 2 (TMPRSS2)) analysis as an assay, we earlier screened several synthetic and natural compounds and identified candidates that showed ability to down-regulate their expression. Here, we report experimental and computational analyses of two small molecules, Mortaparib and MortaparibPlus that were initially identified as dual novel inhibitors of mortalin and PARP-1, for their activity against SARS-CoV-2. In silico analyses showed that MortaparibPlus, but not Mortaparib, stably binds into the catalytic pocket of TMPRSS2. In vitro analysis of control and treated cells revealed that MortaparibPlus caused down-regulation of ACE2 and TMPRSS2; Mortaparib did not show any effect. Furthermore, computational analysis on SARS-CoV-2 main protease (Mpro) that also predicted the inhibitory activity of MortaparibPlus. However, cell-based antiviral drug screening assay showed 30-60% viral inhibition in cells treated with non-toxic doses of either MortaparibPlus or Mortaparib. The data suggest that these two closely related compounds possess multimodal anti-COVID-19 activities. Whereas MortaparibPlus works through direct interactions/effects on the host cell surface receptors (ACE2 and TMPRSS2) and the virus protein (Mpro), Mortaparib involves independent mechanisms, elucidation of which warrants further studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Computational Biology / COVID-19 Topics: Traditional medicine / Vaccines Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: BSR20212156

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Computational Biology / COVID-19 Topics: Traditional medicine / Vaccines Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: BSR20212156