ABSTRACT
At the time of COVID-19 coronavirus pandemia, the Nobel Prize of Physiology or Medicine 2020 was awarded jointly to three researchers Harvey J. Alter, Charles M. Rice, and Michael Houghton for the discovery of Hepatitis C virus. Their works contributed to the isolation of the blood-borne virus, causing chronic hepatitis in 80% of infected person, resulting in cirrhosis, and in elevated risk of liver failure and hepatocellular carcinoma formation. Their results created the basis of HCV screening of blood, and blood products, achieving more than 95% cure of infected people without nearly side effects with direct-acting antiviral agents, supporting the goal of the WHO targeting the elimination of viral hepatitis by 2030.
ABSTRACT
Direct-acting antiviral agents (DAAs) represent a class of drugs targeting viral proteins and have been demonstrated to be very successful in combating viral infections in clinic. However, DAAs suffer from several inherent limitations, including narrow-spectrum antiviral profiles and liability to drug resistance, and hence there are still unmet needs in the treatment of viral infections. In comparison, host targeting antivirals (HTAs) target host factors for antiviral treatment. Since host proteins are probably broadly required for various viral infections, HTAs are not only perceived, but also demonstrated to exhibit broad-spectrum antiviral activities. In addition, host proteins are not under the genetic control of viral genome, and hence HTAs possess much higher genetic barrier to drug resistance as compared with DAAs. In recent years, much progress has been made to the development of HTAs with the approval of chemokine receptor type 5 antagonist maraviroc for human immunodeficiency virus treatment and more in the pipeline for other viral infections. In this review, we summarize various host proteins as antiviral targets from a medicinal chemistry prospective. Challenges and issues associated with HTAs are also discussed.