The genetically diverse Orthocoronavirinae (coronavirus, CoV) family circulates in many avian and mammalian species. CoVs include four 4 genera: alpha (group 1), beta (group 2), gamma (group 3) and delta (group 4). There are three new human CoV in the past 20 years. They are severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012, and now SARS-CoV-2 in 2019. SARS- and MERS-CoV, and SARS-CoV-2 can progress to acute lung injury (ALI), an end-stage lung disease with limited treatment options and very poor prognoses.
SARS-CoV-2 belongs to the Coronavirus genus in the Coronaviridae family and has a positive-sense RNA genome. It uses the angiotensin-converting enzyme 2 (ACE2) as a cellular entry receptor. SARS-CoV-2 shows highly pathogenic, causes severe or even life-threatening diseases, and still transmits from person-to-person. Until now, there do not have effective drugs for the prevention or treatment of COVID-19.
Currently, EIDD-2801 is an orally bioavailable prodrug of the ribonucleoside analog EIDD-1931. It has broad-spectrum antiviral activity against influenza virus and multiple coronaviruses, such as SARS-CoV-2, MERS-CoV, SARS-CoV. EIDD-2801 has the potential for COVID-19, and seasonal and pandemic influenza treatment.
In vivo, 50, 150, or 500 mg/kg EIDD-2801 orally administered in the intranasal infection mouse-adapted SARS-CoV (SARS-MA15). The body weight loss compared to vehicle treatment was significantly diminished (50 mg/kg) or prevented (150, 500 mg/kg) with EIDD-2801 prophylaxis. Therefore, EIDD-2801 is robustly antiviral and able to prevent SARS-CoV replication and disease. Altogether, therapeutic EIDD-2801 is potently antiviral against SARS-CoV in vivo but the degree of clinical benefit was dependent on the time of initiation postinfection.
In summary, EIDD-2801 is a potent broad-spectrum antiviral agent. It is a useful tool for newly emerging coronavirus infections of the future.