ABSTRACT
In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.
ABSTRACT
Aim. The aim of this review is a comprehensive analysis of current literature data on coronaviruses identified in bats. Discussion. Coronaviruses (Coronaviridae) constitute the most extensive family of viruses of the order Nidovirales. Coronaviruses have a wide range of hosts, including mammals (Alpha coronavirus, Betacoronavirus, Deltacoronavirus, Gamn7acoronavirus) and birds (Deltacoronavirus, Garnmacoronavirus), amphibians (Alphaietovirus) and are pathogens of respiratory, intestinal, cardiovascular. Until the beginning of this century, only etiological agents of mild and moderate respiratory diseases were known among pathogenic coronaviruses for humans. In the 21st century, new highly pathogenic coronaviruses were discovered that caused outbreaks of severe pneumonia with high mortality: the severe acute respiratory syndrome coronavirus (Severe acute respiratory syndrome-related coronavirus, SARS-CoV;2002-2003, southern provinces of China), the Middle East respiratory coronavirus Syndrome (Middle East respiratory syndrome-related coronavirus, MERS-CoV;2012, western part of Saudi Arabia) and type 2 acute respiratory syndrome coronavirus (Severe acute respiratory syndrome-related coronavirus 2, SARS-CoV-2;2019 -..., the eastern part of central China). The natural reservoirs of SARS-CoV, SARS-CoV-2 and MERS-CoV are bats (Chiroptera). Coronaviruses circulating in bat populations are not only phylogenetically close to the currently known especially dangerous human viruses but probably have epidemic potential that can be realized in the future. Conclusion. This review presents current data on coronaviruses of bats: taxonomic status, spectrum of potential hosts, distribution. The ecological features of coronaviruses of bats are considered in the context of their epidemiological significance. The origin of pathogenic human coronaviruses is discussed.