Pharmacotherapy of Emerging Antiviral Agents

Anti-infective agents have been one of the greatest accomplishments of modern medicine, which has led to a decrease in the number of deaths caused by various infectious diseases. The anti-infective agents are a broad family consisting of antimicrobials, antifungals, antimalarials, antiprotozoal, antituberculosis, and antiviral agents. Viral infections have caused millions of casualties worldwide, leading to the need for the development of effective antiviral agents. Although the replication mechanism differs significantly between the viruses, all viruses undergo steps like attachment, entry, genome replication, gene expression, and assembly for the release of the virions into the body of the host. Treatment with antiviral agents is essential for blocking the replication of the virus, and the currently available antiviral therapies are directed according to the disease. Furthermore, the treatment with antiviral agents aims to eradicate the viral pathogen from the host and prevent the clinical manifestation. Infectious diseases, such as human immunodeficiency virus (HIV), hepatitis B, and hepatitis C virus (HBV and HCV), and influenza, are of significant global concern. On the contrary, the outbreak of newer strains of influenza virus and Zika virus, Ebola virus, strains of coronavirus (CoV) like severe acute respiratory syndrome (SARS – CoV), Middle East respiratory syndrome (MERS – CoV) and novel Coronavirus (2019-nCoV) are life-threatening viral infections that exhibit major challenges to the humanity. As of date, multiple effective virostatics that target specific viral replication steps are approved for the treatment of viral infections. However, the use of such agents is restricted given the rapid emergence of antiviral resistance, which remains a major concern of current antiviral therapy. In this chapter, we summarize recent antiviral agents that show promising clinical benefits in various phases of clinical trials and also consider them as potential therapeutic agents in the future. Besides, we highlight and analyze the development of novel inhibitors targeting various stages of the viral life cycle that act by distinct mechanisms against current and emerging viral infections. Many antiviral drugs currently available are based on the concept of traditional chemotherapy. Nevertheless, new developments and advances in molecular biology have opened up possibilities to alternate treatment approaches. Clinical trials to evaluate gene silencing mediated by small interfering RNA (siRNA) and antisense RNAs expression against infection with a respiratory syncytial virus (RSV) have recently been initiated. Moreover, in–vitro studies of antisense RNA or siRNA technology have shown promising results in various virus strains. Despite the recent advancements, the development of targeted delivery of antiviral RNA molecules remains a major challenge since DNA viruses and retroviruses can incorporate their genomes into human genomes. To emphasize, antiviral drugs against particular target proteins have been effective in the treatment of prevalent infectious diseases such as HIV and HCV. Thereupon, broad-spectrum antiviral drugs instead of antivirals against specific virus infections need to be designed. With the rapid development of in-silico tools and gene modification strategies, antiviral drugs with better therapeutic index and safety profile will be developed against infectious diseases in the future. In fact, the effective design of newer antiviral drugs will reduce the possibility of emerging antiviral resistance.

Keywords: Antivirals, Clinical trials, Coronavirus, Human immunodeficiency virus, Middle East respiratory syndrome, Pharmacotherapy, Respiratory syncytial virus.