Potential Emergence of Antiviral-Resistant Pandemic Viruses via Environmental Drug Exposure of Animal Reservoirs

摘要

A continuous leak of antiviral drugs into the environment leads to antiviral drug resistance which compromises the treatment of human viral diseases. As the intense search for effective drugs against the novel coronavirus (SARS-CoV-2) is progressing worldwide, several antiviral and antiparasitic drugs, including those for Ebola (remdesivir), influenza (favipiravir, oseltamivir), HIV (lopinavir/ritonavir), and malaria (chlor-oquine), have undergone clinical trials on COVID-19 patients.3'4 Since these drugs and their metabolites are mostly excreted in urine, there is the potential for discharge to the environment depending on removal efficiency at wastewater treatment plants (WWTPs). For example, our preliminary worst-case (treatment by activated sludge process only) estimation shows that rivers and lakes receive 430-2120 ng/ L favipiravir hydroxide, the major metabolite of influenza drug favipiravir (Avigan), or 54-270 ng/L GS-441524, the active form of ebola drug remdesivir, from WWTP effluents if 100 new patients per 1 milllion capita are added every day to existing patients who are treated with the drugs (estimated based on Singer et al. 2008 and Azuma et al. 2012). Animals that are a natural reservoir of viruses, including bats, camels, cats, pangolins, and pigs, may then be exposed to the river water containing antiviral drugs (Figure l), inducing antiviral selective pressures and mutations in the virus leading to antiviral drug resistance.