Preprint Brief Report Version 1 This version is not peer-reviewed

Nsp7 and Spike Glycoprotein of SARS-CoV-2 Are Envisaged as Potential Targets of Vitamin D and Ivermectin

Version 1 : Received: 3 May 2020 / Approved: 5 May 2020 / Online: 5 May 2020 (15:18:30 CEST)

How to cite: Dasgupta, J.; Sen, U.; Bakshi, A.; Dasgupta, A.; Manna, K.; Saha, C.; De, R.K.; Mukhopadhyay, S.; Bhattacharyya, N.P. Nsp7 and Spike Glycoprotein of SARS-CoV-2 Are Envisaged as Potential Targets of Vitamin D and Ivermectin. Preprints 2020, 2020050084 (doi: 10.20944/preprints202005.0084.v1). Dasgupta, J.; Sen, U.; Bakshi, A.; Dasgupta, A.; Manna, K.; Saha, C.; De, R.K.; Mukhopadhyay, S.; Bhattacharyya, N.P. Nsp7 and Spike Glycoprotein of SARS-CoV-2 Are Envisaged as Potential Targets of Vitamin D and Ivermectin. Preprints 2020, 2020050084 (doi: 10.20944/preprints202005.0084.v1).

Abstract

COVID-19 has emerged as deadly pandemic worldwide with no vaccine or suitable antiviral drugs to prevent or cure the disease. Because of the time-consuming process to develop new vaccines or antiviral agents, there has been a growing interest in repurposing some existing drugs to combat SARS-CoV-2. Vitamin D is known to be protective against acute respiratory distress syndrome (ARDS), pneumonia and cytokine storm. Recently it has been used as a repurposed drug for the treatment of H5N1 virus-induced lung injury. Circumstantial evidences indicate that people with low level of vitamin D are more susceptible to SARS-CoV-2. Although, vitamin D was suggested to interfere with viral replication, its interaction with any SARS-CoV-2 protein is unexplored yet. Beside this, ivermectin, a well-known anti-parasitic agent, exhibits potent anti-viral activities in vitro against viruses such as HIV-1 and dengue. Very recently, ivermectin has been found to reduce viral load of SARS-CoV-2 in vitro. We have analyzed available structures of SARS-CoV-2 proteins to identify probable binding partner(s) of vitamin D and ivermectin through knowledge-based docking studies and figured out possible implication of their binding in SARS-CoV-2 infection. Our observations suggest that the non-structural protein nsp7 possesses a potential site to house 25-hydroxyvitamin D3 (VDY) or the active form of Vitamin D, calcitrol. Binding of vitamin D with nsp7 likely to hamper the formation of nsp7-nsp8 complex which is required to bind with RNA dependent RNA polymerase (RdRP), nsp12 for optimal function. On the other hand, potential binding site of ivermectin has been identified in the S2 subunit of trimeric spike(S) glycoprotein of SARS-CoV-2. We propose that deeply inserted mode of ivermectin binding at three inter-subunit junctions may restrict large scale conformational changes of S2 helices which is necessary for efficient fusion of viral and host membrane. Our study, therefore, opens up avenues for further investigations to consider vitamin D and ivermectin as potential drugs against SARS-CoV-2.

Subject Areas

SARS-CoV-2; Vitamin D; Ivermectin; RNA-dependent-RNA polymerase; Spike glycoprotein; Knowledge based docking

Comments (3)

Comment 1
Received: 13 May 2020
The commenter has declared there is no conflict of interests.
Comment: We are working more to validate the results computationally.
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Comment 2
Received: 13 May 2020
The commenter has declared there is no conflict of interests.
Comment: Good work... Is some in vitro/in vivo validation possible?
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Response 1 to Comment 2
Received: 14 May 2020
Commenter: ABHISEK BAKSHI
The commenter has declared there is no conflict of interests.
Comment: We are working more on this. I hope we can show such validation in the near future.

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