Biochemical analysis of packing and assembling heptad repeat motifs in the coronavirus spike protein trimer.

During a coronavirus infection, the spike protein undergoes sequential structural transitions triggered by its receptor and the host protease at the interface between the virus and cell membranes, thereby mediating membrane fusion. After receptor binding, the heptad repeat motif (HR1/HR2) within the viral spike protein bridges the viral and cellular membranes; however, the intermediate conformation adopted by the spike protein when drawing the viral and cellular membranes into close proximity remains unclear due to its transient and unstable nature. Here, we experimentally induced conformational changes in the spike protein of a murine coronavirus by incubating the virus with its receptor, followed by exposure to trypsin.

Frequent occurrence of mutations in nsp3 and nsp4 of SARS-CoV-2, presumably caused by the inhaled asthma drug ciclesonide.

Mutations in nonstructural protein 3 (nsp3) and nsp4 of SARS-CoV-2, presumably induced by the asthma drug ciclesonide (which also has anti-SARS-CoV-2 activity), were counted 5,851 cases in the GISAID EpiCoV genome database. Sporadic occurrence of mutants not linked to each other in the phylogenetic tree were identified at least 88 times; of which, 58 had one or more descendants in the same branch. Five of these had spread to more than 100 cases, and one had expanded to 4,748 cases, suggesting the mutations are frequent, selected in individual patients, and transmitted to form clusters of cases.