DRUG RESISTANCE IN FOUR IMPORTANT HUMAN VIRUSES: UPDATED REVIEW

Viruses causes severe infections and associated and linked with outbreaks of some major global diseases such as HIV/AIDS, COVID-19, influenza virus, dengue fever, common cold, and hepatitis. The infective process of viruses varies depending on the viral species; however, they follow certain steps in the infective process. The typical stages in their life cycle include (Fig 1): attachment and entry, viral uncoating, replication and transcription of viral genome, protein synthesis, assembly, and release of progeny virus. Antiviral drugs are used in combating viral infections and the development of these drugs has been major achievement in the global effort to mitigate infectious diseases. Antiviral drugs are available for a number of viruses including severe acute respiratory coronavirus 2 (SARS-CoV-2), hepatitis-A and-B virus, influenza virus, Papillomavirus. Human Immunodeficiency Virus (HIV), respiratory synctial virus, human cytomegalovirus (HCMV). Although most of these agents are not curative, they can efficiently control viral replications. They can be either small or large molecules, synthetic or natural. Based on their mode of action (MOA), antiviral agents are divided into two classes: 1, inhibitors of the viruses or 2. Inhibitors of the target host cells. Viral –targeting antivirals (VTAs) act by either directly or indirectly inhibiting the biological functions of viral protein which results in the inhibition of the ideal viral replication machinery. Host-targeting antivirals (HATs) on the other hand target the host protein that are associated with the viral replication cycle, regulating the function of the immune system or other cellular processes in the host (3) The Food & Drug Administration Board has approved more than hundred antiviral agents which are based on either monotherapy and combined therapies (https://www.fda.gov). The approved drugs have different MOAs based on their functions or structures. These includes structural analogues, entry inhibitors, integrase inhibitors, essential enzyme inhibitors such as nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, inhibitors that are specific to certain viruses such as influenza virus and HCV NS5A protein and NS5B polymerase inhibitors, immunomodulators, interferons, antimitotic inhibitors, and oligonucleotides