A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.

Diagnosis, treatment, control and prevention of SARS-CoV-2 and coronavirus disease 2019: back to the future / 生物工程学报

The ongoing outbreak of the coronavirus disease 2019 (COVID-19) as named by the World Health Organization has millions of confirmed cases around the world and has claimed hundreds of thousands of lives. The virus was named SARS-CoV-2 in February by International Committee on Taxonomy of Viruses. COVID-19 presents as fever, dry cough, dyspnea, headache and pneumonia. In a small subset of severe cases, the disease quickly progresses to respiratory failure and even death. Since the 21st century, there have been three major outbreaks caused by human coronaviruses, including the severe acute respiratory syndrome (SARS) that broke out in 2003, the Middle East respiratory syndrome (MERS) in 2012, and the recent pandemic of COVID-19. Since 2003, significant progress has been made in the study of SARS-CoV and MERS-CoV concerning their natural origins, pathogenesis, antiviral development and vaccine design. Since SARS-CoV-2 and SARS-CoV are closely related, previous findings on SARS-CoV are highly relevant to a better understanding as well as diagnosis, treatment, prevention and control of SARS-CoV-2. In this review, we highlight recent progresses in the field; compare the biological characteristics of SARS-CoV and SARS-CoV-2; summarize the urgently-needed diagnostic, treatment, prevention and control options; and provide future perspectives for the outcome of the outbreak and research questions to be answered, including some of the difficulties in vaccine development. Hopefully, our comments and suggestions would prove useful for the control of the SARS-CoV-2 epidemic in China and the world.