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In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of global concern – causing severe respiratory illness with 97 confirmed cases and 46 deaths1. Therapeutic interventions have not been evaluated in vivo, thus patient management relies exclusively on supportive care, which given the high case-fatality rate is not highly effective. The rhesus macaque is the only known disease model for MERS-CoV, developing an acute localized-to-widespread pneumonia with transient clinical disease2,3 that recapitulates mild-to-moderate human MERS-CoV cases4,5. The combination of interferon-α2b and ribavirin was effective in reducing MERS-CoV replication in vitro6; therefore, this strategy was initiated 8 h post-infection in the rhesus macaque model. Treated animals did not develop breathing abnormalities and showed no-to-very mild radiographic evidence of pneumonia. Moreover, treated animals showed reduced levels of systemic (serum) and local (lung) proinflammatory markers in addition to reduced viral genome copies, altered gene expression and less severe histopathological changes in the lungs. Taken together, these data suggest that treatment of MERS-CoV infected rhesus macaques with IFN-α2b and ribavirin reduces virus replication, moderates the host response and improves clinical outcome. As these two drugs are already used in combination in the clinic, IFN-α2b and ribavirin should be considered for management of MERS-CoV cases.

Since the first reports of a novel SARS-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how SARS-CoV-2 emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.