COVID-19 pandemic caused by 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 compound/s 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 downregulate 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 downregulation 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 anti-virus drug screening assay showed 30~60% viral inhibition in cells treated with non-toxic doses of either MortaparibPlus or Mortaparib. The data suggests 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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Research Article|
October 04 2021
Computational and in vitro experimental analyses of the Anti-COVID-19 potential of Mortaparib and MortaparibPlus
Vipul Kumar;
Vipul Kumar
Indian Institute of Technology Delhi, New Delhi, India
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Anissa Nofita Sari;
Anissa Nofita Sari
National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan
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Hazna Noor Meidinna;
Hazna Noor Meidinna
National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan
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Jaspreet Kaur Dhanjal;
Jaspreet Kaur Dhanjal
Indraprastha Institute of Information Technology Delhi, New Delhi, India
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Chandru Subramani;
Chandru Subramani
Regional Centre for Biotechnology, Faridabad, India
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Brohmomoy Basu;
Brohmomoy Basu
Regional Centre for Biotechnology, Faridabad, India
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Sunil C Kaul;
Sunil C Kaul
National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan
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Sudhanshu Vrati;
Sudhanshu Vrati
Regional Centre for Biotechnology, Faridabad, India
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Durai Sundar;
Indian Institute of Technology Delhi, New Delhi, India
* Corresponding Author; email: sundar@dbeb.iitd.ac.in
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Renu Wadhwa
Renu Wadhwa
National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Japan
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Publisher: Portland Press Ltd
Received:
September 08 2021
Revision Received:
September 11 2021
Accepted:
October 04 2021
Online ISSN: 1573-4935
Print ISSN: 0144-8463
Copyright 2021 The Author(s)
2021
This is an Accepted Manuscript; not the final Version of Record. You are encouraged to use the final Version of Record that, when published, will replace this manuscript and be freely available under a Creative Commons licence.
Biosci Rep (2021) BSR20212156.
Article history
Received:
September 08 2021
Revision Received:
September 11 2021
Accepted:
October 04 2021
Citation
Vipul Kumar, Anissa Nofita Sari, Hazna Noor Meidinna, Jaspreet Kaur Dhanjal, Chandru Subramani, Brohmomoy Basu, Sunil C Kaul, Sudhanshu Vrati, Durai Sundar, Renu Wadhwa; Computational and in vitro experimental analyses of the Anti-COVID-19 potential of Mortaparib and MortaparibPlus. Biosci Rep 2021; BSR20212156. doi: https://doi.org/10.1042/BCJ20210626
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