of some patients in Wuhan might be linked to misuse of steroids. Nevertheless, the screening of new pharmaceuticals, smallmolecule compounds and other agents that have potent anti-SARS-CoV-2 efects will successfully derive new and better lead compounds and agents that might prove useful in the treatment of COVID-19. Te seventh question is whether inactivated vaccines are a viable option for SARS-CoV-2. Te chance that SARS-CoV-2 will become endemic in some areas or even pandemic has increased in view of its high transmissibility, asymptomatic and presymptomatic virus shedding, high number of patients with mild symptoms, as well as the evidence for superspreading events. Tus, vaccine development becomes necessary for prevention and ultimate eradication of SARS-CoV-2. Inactivated vaccines are one major type of conventional vaccines that could be easily produced and quickly developed. In this approach, SARS-CoV-2 virions can be chemically and/or physically inactivated to elicit neutralizing antibodies. In the case of SARS-CoV and MERS-CoV, neutralizing antibodies were successfully and robustly induced by an inactivated vaccine in all types of animal experiments, but there are concerns about antibody-dependent enhancement of viral infection and other safety issues. While inactivated vaccines should still be tested, alternative approaches Yuen et al. Cell Biosci (2020) 10:40 Page 4 of 5 include live attenuated vaccines, subunit vaccines and vectored vaccines. All of these merit further investigations and tests in animals. Te eighth question relates to the origins of SARSCoV-2 and COVID-19. To make a long story short, two parental viruses of SARS-CoV-2 have now been identifed. Te frst one is bat coronavirus RaTG13 found in Rhinolophus afnis from Yunnan Province and it shares 96.2% overall genome sequence identity with SARSCoV-2 [3]. However, RaTG13 might not be the immediate ancestor of SARS-CoV-2 because it is not predicted to use the same ACE2 receptor used by SARS-CoV-2 due to sequence divergence in the receptor-binding domain sharing 89% identity in amino acid sequence with that of SARS-CoV-2. Te second one is a group of betacoronaviruses found in the endangered species of small mammals known as pangolins [4], which are often consumed as a source of meat in southern China. Tey share about 90% overall nucleotide sequence identity with SARS-CoV-2 but carries a receptor-binding domain predicted to interact with ACE2 and sharing 97.4% identity in amino acid sequence with that of SARS-CoV-2. Tey are closely related to both SARS-CoV-2 and RaTG13, but apparently they are unlikely the immediate ancestor of SARSCoV-2 in view of the sequence divergence over the whole genome. Many hypotheses involving recombination, convergence and adaptation have been put forward to suggest a probable evolutionary pathway for SARS-CoV-2, but none is supported by direct evidence. Te jury is still out as to what animals might serve as reservoir and intermediate hosts of SARS-CoV-2. Although Huanan seafood wholesale market was suggested as the original source of SARS-CoV-2 and COVID-19, there is evidence for the involvement of other wild animal markets in Wuhan. In addition, the possibility for a human superspreader in the Huanan market has not been excluded. Further investigations are required to shed light on the origins of SARSCoV-2 and COVID-19. Te ninth question concerns why SARS-CoV-2 is less pathogenic. If the reduced pathogenicity of SARS-CoV-2 is the result of adaptation to humans, it will be of great importance to identify the molecular basis of this adaptation. Te induction of a cytokine storm is the root cause of pathogenic infammation both in SARS and COVID19. SARS-CoV is known to be exceedingly potent in the suppression of antiviral immunity and the activation of proinfammatory response. It is therefore intriguing to see how SARS-CoV-2 might be diferent from SARS-CoV in interferon-antagonizing and infammasome-activating properties. It is noteworthy that some interferon antagonists and infammasome activators encoded by SARSCoV are not conserved in SARS-CoV-2. Particularly, ORF3 and ORF8 in SARS-CoV-2 are highly divergent from ORF3a and ORF8b in SARS-CoV that are known to induce NLRP3 infammasome activation. ORF3 of SARS-CoV-2 is also signifcantly diferent from the interferon antagonist ORF3b of SARS-CoV. Tus, these viral proteins of SARS-CoV and SARS-CoV-2 should be compared for their abilities to modulate antiviral and proinfammatory responses. Te hypothesis that SARS-CoV-2 might be less efcient in the suppression of antiviral response and the activation of NLRP3 infammasome should be tested experimentally. Much progress has been made in the surveillance and control of infectious diseases in China after the outbreak of SARS-CoV in 2003. Meanwhile, virological research in the country has also been strengthened. Te new disease report and surveillance system did function relatively well during the 2009 pandemic of swine fu. New viral pathogens such as avian infuenza virus H7N9 and severe-fever-with-thrombocytopenia syndrome bunyavirus have also been discovered in recent years [11, 12], indicating the strength and vigor of Chinese infectious disease surveillance and virological research. However, the ongoing outbreak of SARS-CoV-2 has not only caused