A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

Madan, T.; Biswas, B.; Varghese, P.; Subedi, R.; Pandit, H.; Idicula-Thomas, S.; Kundu, I.; Rooge, S. B.; Aggarwal, R.; Tripathi, D.; Kaur, S.; Gupta, E.; Gupta, S.; Kishore, U.

doi:10.1101/2020.12.18.423415

bioRxiv · 10.1101/2020.12.18.423415

A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples

Madan, T.·Biswas, B.·Varghese, P.·Subedi, R.·Pandit, H.·Idicula-Thomas, S.·Kundu, I.·Rooge, S. B.·Aggarwal, R.·Tripathi, D.·Kaur, S.·Gupta, E.·Gupta, S.·Kishore, U.

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Abstract

RationaleCOVID-19 is an acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human surfactant protein D (SP-D) is known to interact with spike protein of SARS-CoV, but its immune-surveillance against SARS-CoV-2 is not known. ObjectiveThis study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. MethodsrfhSP-D interaction with spike protein of SARS-CoV-2 and hACE-2 receptor was predicted via docking analysis. The inhibition of interaction between spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was studied by measuring the expression of RdRp gene of the virus using qPCR. Measurements and Main ResultsIn-silico interaction studies indicated that three amino acid residues in the RBD of spike of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2 positive cases (asymptomatic, n=7 and symptomatic, n=8 and negative controls n=15) demonstrated that treatment with 5M rfhSP-D inhibited viral replication by ~5.5 fold and was more efficient than Remdesivir (100 M). Approximately, a 2-fold reduction in viral infectivity was also observed after treatment with 5M rfhSP-D. ConclusionsThese results conclusively demonstrate that the calcium independent rfhSP-D mediated inhibition of binding between the receptor binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and a significant reduction in SARS-CoV-2 infection and replication in-vitro.

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Madan, T., Biswas, B., Varghese, P., Subedi, R., Pandit, H., Idicula-Thomas, S., Kundu, I., Rooge, S. B., Aggarwal, R., Tripathi, D., Kaur, S., Gupta, E., Gupta, S., Kishore, U.. 2020-12-18. A recombinant fragment of Human surfactant protein D binds Spike protein and inhibits infectivity and replication of SARS-CoV-2 in clinical samples. https://doi.org/10.1101/2020.12.18.423415

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