The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug-and infectioninduced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anticytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and 2 of 19 | WANG et Al. 1 | INTRODUCTION Coronavirus disease-19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus SARS-CoV2 that has reached global pandemic status and become a major global health threat. As of December 1 2020, there have been 63,751,931 confirmed cases and 1,477,976 deaths worldwide. 1 The United States hit record-high daily COVID-19 cases in November, 2020. Since the pandemic started in March, 2020, the nation has surpassed 12 million cases and more than 266,000 Americans have died. United States could see "a surge upon a surge" of COVID-19 cases this winter. 2 During just two full days at the end of November, 2020, the country saw over 360,000 new COVID-19 cases nationwide, in addition to over 2,700 new deaths. In 2003, a zoonotic coronavirus outbreak of SARS-CoV had resulted in severe SARS with fatality rates of 10%. 3-6 The SARS-CoV-2 genome shares approximately 70%-80% sequence similarity to SARS-CoV, and causes similar clinical symptoms. 7,8 Key clinical features of COVID-19 and SARS include fever, chills, muscle pain, headache, sore throat, new loss of taste or smell, cough, shortness of breath, gastrointestinal problems in mild to moderate cases, and more serious disease involving pneumonia, acute respiratory distress syndrome, cardiovascular and hepatic failure with high morbidity. 7,8 Individuals with pre-existing conditions like cardiovascular disease, hypertension, asthma, and diabetes, 9 and elderly patients are at a higher risk to become infected with severe symptoms. 10 To date, no specific therapeutic drug or vaccine COVID-19 and SARS is available, resulting in an urgent need for broad-spectrum therapeutics for COVID-19 and other CoV infections.
