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Abstract Nanobodies, single-domain antibodies derived from variable domain of camelid or shark heavy-chain antibodies, have unique properties with small size, strong binding affinity, easy construction in versatile formats, high neutralizing activity, protective efficacy, and manufactural capacity on a large-scale. Nanobodies have been arisen as an effective research tool for development of nanobiotechnologies with a variety of applications. Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, have caused serious outbreaks or a global pandemic, and continue to post a threat to public health worldwide. The viral spike (S) protein and its cognate receptor-binding domain (RBD), which initiate viral entry and play a critical role in virus pathogenesis, are important therapeutic targets. This review describes pathogenic human CoVs, including viral structures and proteins, and S protein-mediated viral entry process. It also summarizes recent advances in development of nanobodies targeting these CoVs, focusing on those targeting the S protein and RBD. Finally, we discuss potential strategies to improve the efficacy of nanobodies against emerging SARS-CoV-2 variants and other CoVs with pandemic potential. It will provide important information for rational design and evaluation of therapeutic agents against emerging and reemerging pathogens. Graphical abstract

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broadspectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. There is worldwide concern about the new coronavirus 2019-nCoV as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. Determining the origin and evolution of 2019-nCoV is important for the surveillance, drug discovery, and prevention of the epidemic. With more and more reported pathogenic 2019-nCoV isolates, it is necessary to re examne their origin and diversification patterns. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; pathogenic coronaviruses; SARS-CoV; MERS-CoV; SARS-CoV-2; origin; evolution EN COVID-19 pathogenic coronaviruses SARS-CoV MERS-CoV SARS-CoV-2 origin evolution 1 3 3 04/24/20 20200421 NES 200421 One of major study concerns in virology is viral adaptive evolution due to its highly replicable and mutable nature in changeable environments. Among viruses, some coronaviruses (CoVs) are notorious for causing the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). (2020) 382: 727-33. 10.1056/NEJMoa200101731978945 4 Lau, SKP, Feng, Y, Chen, H, Luk, HKH, Yang, W-H, Li, KSM, Severe Acute Respiratory Syndrome (SARS) coronavirus ORF8 protein is acquired from SARS-related coronavirus from greater horseshoe bats through recombination. [Extracted from the article]