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23 results on '"Rajpoot, Sajjan"'

11. Investigating theobromine as a potential anti‐human coronaviral agent.

Author

Li, Jiajing, Wang, Yining, Rajpoot, Sajjan, Lavrijsen, Marla, Pan, Qiuwei, Li, Pengfei, and Baig, Mirza S.

Subjects
CORONAVIRUS diseases, COVID-19, CORONAVIRUSES, MOLECULAR docking, COVID-19 vaccines, ANTIVIRAL agents
Abstract

Coronaviruses (CoVs) have long been known to infect humans, mainly alpha‐CoV and beta‐CoV. The vaccines developed for SARS‐CoV‐2 are likely not effective against other coronavirus species, whereas the risk of the emergence of new strains that may cause the next epidemic/pandemic is high. The development of antiviral drugs that are effective across different CoVs represents a viable strategy for improving pandemic preparedness. In this study, we aim to identify pan‐coronaviral agents by targeting the conserved main protease (Mpro). For drug screening, the catalytic dyad of four human CoVs (HCoVs: SARS‐CoV‐2, and seasonal CoV NL63, OC43, and 229E) was targeted by molecular docking. The identified leading candidate theobromine, a xanthine derivative, was further tested in cell culture models of coronavirus infection. Theobromine binds strongly with the catalytic dyad (His41 and Cys144/145) of SARS‐CoV‐2 and HCoV‐NL63 Mpro, mildly with HCoV‐OC43, but not with HCoV‐229E. However, theobromine only shows dose‐dependent inhibition in Calu3 cells inoculated with SARS‐CoV‐2, but not in cells inoculated with seasonal CoVs. Theobromine exerts antiviral activity against coronavirus infections potentially through targeting Mpro. However, the antiviral potency is distinct among different CoVs. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Repurposing dyphylline as a pan-coronavirus antiviral therapy

Author

Wang, Yining, Rajpoot, Sajjan, Li, Pengfei, Lavrijsen, Marla, Ma, Zhongren, Hirani, Nik, Saqib, Uzma, Pan, Qiuwei, Baig, Mirza S, Wang, Yining, Rajpoot, Sajjan, Li, Pengfei, Lavrijsen, Marla, Ma, Zhongren, Hirani, Nik, Saqib, Uzma, Pan, Qiuwei, and Baig, Mirza S

Abstract

Background: In the last two decades, the world has witnessed the emergence of zoonotic corona viruses (CoVs), which cause mild to severe respiratory diseases in humans. Human coronaviruses (HCoVs), mainly from the alpha-CoV and beta-CoV genera, have evolved to be highly pathogenic, such as SARS-CoV-2 causing the COVID-19 pandemic. These coronaviruses carry functional enzymes necessary for the virus life cycle, which represent attractive antiviral targets. Methods & Results: We aimed to therapeutically target the main protease (Mpro) of HCoV-NL63 and HCoV-229E (from alpha-CoV genus) and HCoV-OC43 and SARS-CoV-2 (from beta-CoV genus). Through virtual screening, we identified an FDA-approved drug dyphylline, a xanthine derivate, that binds to the catalytic dyad residues; histidine and cystine of the Mpro structures. Importantly, dyphylline dose-dependently inhibited the viral replication in cell culture models infected with the viruses. Conclusion: Our findings support the repurposing of dyphylline as a pan-coronavirus antiviral agent.

Published
2022

16. Structural analysis of spike proteins from SARS-CoV-2 variants of concern highlighting their functional alterations

Author

Solanki, Kundan, Rajpoot, Sajjan, Kumar, Ashutosh, J Zhang, Kam Y, Ohishi, Tomokazu, Hirani, Nik, Wadhonkar, Khandu, Patidar, Pramod, Pan, Qiuwei, Baig, Mirza S, Solanki, Kundan, Rajpoot, Sajjan, Kumar, Ashutosh, J Zhang, Kam Y, Ohishi, Tomokazu, Hirani, Nik, Wadhonkar, Khandu, Patidar, Pramod, Pan, Qiuwei, and Baig, Mirza S

Abstract

Aim: Mutations in the SARS-CoV-2 spike (S) protein have dramatically changed the transmissibility and pathogenicity of the virus. Therefore, we studied the binding affinity of Omicron spike-receptor binding domain (S-RBD) with human ACE2 receptor. Materials & methods: We used pyDockWEB and HADDOCK 2.4 docking for our study. Results: Computational docking indicated higher binding affinity of Omicron S-RBD as compared with wild-type SARS-CoV-2 and Delta S-RBD with ACE2. Interface analysis suggested four mutated residues of Omicron S-RBD for its enhanced binding. We also showed decreased binding affinity of Omicron and Delta S-RBDs with monoclonal antibodies. Conclusion: Compared with wild-type SARS-CoV-2, Omicron S-RBD exhibit higher binding with ACE2 and lower affinity against monoclonal antibodies.

Published
2022

19. TIRAP in the Mechanism of Inflammation

Author

Rajpoot, Sajjan, primary, Wary, Kishore K., additional, Ibbott, Rachel, additional, Liu, Dongfang, additional, Saqib, Uzma, additional, Thurston, Teresa L. M., additional, and Baig, Mirza S., additional

Published
2021
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22. Dual targeting of 3CLproand PLproof SARS-CoV-2: A novel structure-based design approach to treat COVID-19

Author

Rajpoot, Sajjan, Alagumuthu, Manikandan, and Baig, Mirza S.

Abstract

With the rapid growth of the COVID-19 (coronavirus disease 2019) pandemic across the globe, therapeutic attention must be directed to fight the novel severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, developing new antiviral drugs and vaccines is time-consuming, so one of the best solutions to tackle this virus at present is to repurpose ready-to-use drugs. This paper proposes the repurposing of the Food and Drug Administration (FDA)-approved, purchasable, and naturally occurring drugs for preventive and therapeutic use. We propose to design a dual-inhibitor for the SARS-CoV-2 cysteine proteases—3 Chemotrypsin-like protease or main protease (3CLproor Mpro) and Papain-like protease (PLpro) responsible for processing the translated polyprotein chain from the viral RNA yielding functional viral proteins. For virtual screening, an unbiased blind docking was performed from which the top nine dual-targeting inhibitors for 3CLproand PLprowere selected. The nine repurposed drugs, block the catalytic dyad (His41 and Cys145) of 3CLproas well as the catalytic triad (Cys111, His272, and Asp286) of PLpro. Repurposing known drugs will not only pave the way for rapid in-vitro and in-vivo studies to battle the SARS-CoV-2 but will also expedite the quest for a potent anti-coronaviral drug.

Published
2021
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