During the first waves of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one of the front-line protections against viral infections, and the immune responses of the nasal mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: the infection of sustentacular cells and the inflammatory reaction of the nasal epithelium. The former triggers OD and the latter likely prolongs OD. These two alternative mechanisms may act in parallel; the infection of sustentacular cells is more important for OD occurrence because sustentacular cells are more likely to be the entry point of SARS-CoV-2 than olfactory neurons and more susceptible to early injury. Furthermore, sustentacular cells abundantly express transmembrane protease, serine 2 (TMPRSS2) and play a major role in the olfactory epithelium. OD occurrence in COVID-19 has revealed crucial roles of sustentacular cells. This review aims to elucidate how immune responses of the nasal epithelium contribute to COVID-19–related OD. Understanding the underlying immune mechanisms of the nasal epithelium in OD may aid in the development of improved medical treatments for COVID-19–related OD.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although unprecedented efforts are underway to develop therapeutic strategies against this disease, scientists have acquired only a little knowledge regarding the structures and functions of the CoV replication and transcription complex (RTC). Ascertaining all the RTC components and the arrangement of them is an indispensably step for the eventual determination of its global structure, leading to completely understanding all of its functions at the molecular level.Results: The main results include: 1) hairpins containing the canonical and non-canonical NSP15 cleavage motifs are canonical and non-canonical transcription regulatory sequence (TRS) hairpins; 2) TRS hairpins can be used to identify recombination regions in CoV genomes; 3) RNA methylation participates in the determination of the local RNA structures in CoVs by affecting the formation of base pairing; and 4) The eventual determination of the CoV RTC global structure needs to consider METTL3 in the experimental design.Conclusions: In the present study, we proposed the theoretical arrangement of NSP12-15 and METTL3 in the global RTC structure and constructed a model to answer how the RTC functions in the jumping transcription of CoVs. As the most important finding, TRS hairpins were reported for the first time to interpret NSP15 cleavage, RNA methylation of CoVs and their association at the molecular level. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, providing a crucial basis for future studies.

In December 2019, the world awoke to a new zoonotic strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the present study, we classified betacoronavirus subgroup B into the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters, and the ORF8 genes of these three clusters into types 1, 2 and 3, respectively. One important result of our study is that the recently reported strain RmYN02 was identified as a recombinant SARS2-like CoV strain that belongs to the SARS-CoV-2 cluster, but has an ORF8 from a SARS-like CoV. This result provides substantial proof for long-existing hypotheses regarding the recombination and biological functions of ORF8. Based on the analysis of recombination events in the Spike gene, we propose that the Spike protein of SARS-CoV-2 may have more than one specific receptor for its function as gp120 of HIV has CD4 and CCR5. We concluded that the furin protease cleavage site acquired by SARS-CoV-2 may increase the efficiency of viral entry into cells, while the type 2 ORF8 acquired by SARS-CoV may increase its replication efficiency. These two most critical events provide the most likely explanation for SARS and COVID-2019 pandemics.