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The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.

Drug combination is a common method for clinical disease treatment. Whether the combination of drugs is reasonable often affects the result of the disease treatment. Many methods have been used to evaluate interaction between drugs to date. Isobologram analysis has been mathematically proven and widely used to evaluate drug interactions. In this paper, the principle of isobologram analysis and its application in drug interaction evaluation are summarized. The applications of the similar cotoxicity coefficient and fractional inhibitory concentration index in the evaluation of drug interaction are also reviewed. This work is expected to evaluate the effect of formulations scientifically and provide scientific judgment standards for the development of formulations and clinical drug compatibility.

Development of non-noble metal electrocatalysts for hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) in acid is a great challenge for the development of polymer electrolyte membrane water electrolysis (PEMWE) and polymer electrolyte membrane fuel cells (PEMFC). Here, we report an efficient strategy for modulating the electron density of MoO2 by Ni doping to accelerate HER and HOR in acid. This is particularly important for PEMWE, PEMFC, and regenerative fuel cells. X-ray absorption spectroscopy demonstrates that Ni is doped by replacing Mo atoms in MoO2. Then Ni doping can lead to electron deficiency on neighboring O sites, which are induced to adsorb hydrogen and then increase the surface hydrogen coverage. Therefore, the doping of Ni can modulate the electron density of MoO2 for accelerating HER and HOR. Our results indicate that the incorporation of a high-electronegativity transition metal into MoO2 provides a new strategy for replacing Pt as an electrocatalyst for HER and HOR in acid.

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