About: Spike protein mutational landscape in India: Could Muller’s ratchet be a future game-changer for COVID-19?

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Spike protein mutational landscape in India: Could Muller’s ratchet be a future game-changer for COVID-19?
Creator	Banerjee, Rachana Basak, Kausik Chattopadhyay, Sujay Ganguly, Debabani Ghosh, Anamika Rajachandran, Vyshakh Sureka, Kamakshi
Source	BioRxiv
abstract	The dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020, and detected the spike protein variants to emerge from two major ancestors – Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein – host receptor (S-R) complexes for these variants correlated strongly (R2=0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 – June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India. Significance Epidemiological features are intricately linked to evolutionary diversity of rapidly evolving pathogens, and SARS-CoV-2 is no exception. Our work suggests the potential of average stability of complexes formed by the circulating spike mutational variants and the human host receptor to track the severity of SARS-CoV-2 infection in a given region. In India, the stability of these complexes for recent variants tend to decrease relative to their ancestral ones, following countrywide declining fatality rate, in contrast to an increasing mutation rate. We hypothesize such a scenario as nascent footprints of Muller’s ratchet, proposing large-scale population genomics study for its validation, since this understanding could lead to therapeutic approaches for facilitating mutational meltdown of SARS-CoV-2, as experienced earlier for influenza A virus.
has issue date	2020-08-18(xsd:dateTime)
bibo:doi	10.1101/2020.08.18.255570
has license	biorxiv
sha1sum (hex)	98b75de0c37d525cc85189a730a4ae959e528e3e
schema:url	https://doi.org/10.1101/2020.08.18.255570
resource representing a document's title	Spike protein mutational landscape in India: Could Muller’s ratchet be a future game-changer for COVID-19?
schema:publication	bioRxiv
resource representing a document's body	covid:98b75de0c37d525cc85189a730a4ae959e528e3e#body_text
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