Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius’ Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia)

Abstract

Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius’ pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score −320.15) and the E. europaeus (docking score –294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.

Intestinal Tropism of a Betacoronavirus ( Merbecovirus ) in Nathusius’s Pipistrelle Bat ( Pipistrellus nathusii ), Its Natural Host

“…The cellular receptors used by PN-βCoV are currently unknown. However, in silico and phylogenetic analysis suggests that this virus might have affinity for bat DPP4 ( 49 ). DPP4 expression has been demonstrated in epithelial cells of the intestinal tract, but not in the respiratory tract, in a species closely related to Nathusius’s Pipistrelle Bats ( 50 ).…”

Multiple independent acquisitions of ACE2 usage in MERS-related coronaviruses

“…Recently, two novel bat merbecoviruses with complete genome sequenced, MOW-15-22 and PN-βCoV (designated PnNL2018B in this study), were independently reported by research teams in Russia and Netherlands 35,36 (Fig. 1a).…”

“…In our quest to identify receptors for representative merbecoviruses, we noticed these two viruses form a distinct clade and exhibited an unknown receptor usage. At the complete-genome level, MOW-15-22 and PnNL2018B share less genetic similarity with the African bat coronaviruses NeoCoV and PDF-2180 but show greater genetic homology with a Italian bat merbecovirus (Hsavll/ltaly/206645-40/2011) and a DPP4-using virus HKU25 35,40 ( Fig. 1c ).…”

“…3 MOW-15-22 and PN-βCoV are two bat merbecoviruses recently identified in P. nathusii bats, a bat species commonly found in Europe 35,36 . To avoid confusion, we designated a specific virus of PN-βCoV (Betacoronavirus sp.…”

“…Previous studies have suggested that HKU5 and HKU31 may not use DPP4 or ACE2 as their receptors, leaving their entry receptor identities to be determined. MOW-15-22 and PN-βCoV are two bat merbecoviruses recently identified in P. nathusii bats, a bat species commonly found in Europe 35,36 . To avoid confusion, we designated a specific virus of PN-βCoV (Betacoronavirus sp.…”