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3. WUHAN LABORATORIES, BAT RESEARCH AND BIOSAFETY

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This is the third part of a series of reports based on our previously unpublished investigations into the origins of SARS-COV-2. We wish to thank all of the independent researchers who have contributed to this investigation, especially members of the DRASTIC Collective, many of whom wish to remain anonymous for reasons of security and privacy (PDF) 3. WUHAN LABORATORIES, BAT RESEARCH AND BIOSAFETY.
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A coronavirus (CoV) commonly known as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and causing COVID-19 (coronavirus disease of 2019) has become a pandemic following an outbreak in Wuhan. Although mutations in the SARS-CoV-2 spike glycoprotein (SGP) are obvious from comparative genome studies, the novel infectious nature of the virus, its new varients detected in the UK, and outside and recovery–death ratios of COVID-19 inspired us to review the mechanisms of the infection, replication, release, and transmission of progeny virions and the immune response in the host cell. In addition to the specificity of SARS-CoV-2 binding to angiotensin-converting enzyme 2 receptor and transmembrane protease serine 2, the varied symptoms and severity of the infection by the original and mutated forms of the virus suggest the significance of correlating the host innate and adaptive immunity with the binding of the virus to the mannose receptor via lipopolysaccharides (LPSs), toll-like receptors via LPS/proteins/RNA, and sialic acid (Sia) via hemagglutinin, or sugar-acid segments of glycans. HA-to-Sia binding is considered based on the innate Sia N-acetylneuraminic acid and the acquired Sia N-glycolylneuraminic acid in the epithelial cells and the sialidase/neuraminidase- or esterase-hydrolyzed release and transmission of CoVs. Furthermore, the cytokine storms common to aged humans infected with SARS-CoV-2 and aged macaques infected with SARS-CoV encourage us to articulate the mechanism by which the nuclear capsid protein and RNAs bypass the pattern recognition-induced secretion of interferons (IFNs), which stimulate IFN genes through the Janus-activated kinase-signal transducer and activator of a transcription pathway, leading to the secretion of antiviral proteins such as myxovirus resistance protein A/B. By considering the complexities of the structure, and the infectious nature of the virus and the structures and functions of the molecules involved in CoV infection, replication, and immune response, a new interface among virology, immunology, chemistry, imaging technology, drug delivery, and nanoscience is proposed and will be developed. This interface can be an essential platform for researchers, technologists, and physicians to collaborate and develop vaccines and medicines against COVID-19 and other pandemics in the future. Scientists in Japan have reviewed how nanoscience is helping us understand infection with SARS-CoV-2, the virus responsible for Covid-19, and the immune response it produces. The coronavirus pandemic has driven international scientific collaboration to identify treatments and develop a vaccine, not only between virologists and immunologists but also with researchers from a broad range of other disciplines including chemists, physicists and materials scientists. Vasudevanpillai Biju from Hokkaido University, Sapporo, and colleagues have reviewed the ongoing research at the interface of infectious diseases, biological chemistry and nanoscience aimed at answering key questions on how the virus functions. The authors summarize the use of nanomaterials in imaging techniques, vaccine development and drug delivery, while investigating problems associated with the toxicity of nanomaterials. Understanding these molecular interactions will help to fight this and future pandemics. Despite the hopeful signs of progress of COVID-19 vaccine development and vaccination, the highly infectious nature and mutations of SARS-CoV-2 are warnings of an infighting annual revival of the virus. This article clarifies the complexities of COVID-19 by referring to the molecular-level mechanisms of the infection, immune response, replication, and transmission of SARS-CoV-2, which are essential during the development of an effective vaccine or a drug to fight the pandemic. Furthermore, this article underscores the significance of an interface among chemistry, nanoscience, cell biology, immunology, and virology to resolve the challenges of COVID-19.
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2–related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.
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