Antiviral therapies: advances and perspectives

Abstract

Viral infections cause high morbidity and mortality, threaten public health, and impose a socioeconomic burden. We have seen the recent emergence of SARS‐CoV‐2 (Severe Acute Respiratory Syndrome Coronavirus 2), the causative agent of COVID‐19 that has already infected more than 29 million people, with more than 900 000 deaths since its identification in December 2019. Considering the significant impact of viral infections, research and development of new antivirals and control strategies are essential. In this paper, we summarize 96 antivirals approved by the Food and Drug Administration between 1987 and 2019. Of these, 49 (51%) are used in treatments against human immunodeficiency virus (HIV), four against human papillomavirus, six against cytomegalovirus, eight against hepatitis B virus, five against influenza, six against herpes simplex virus, 17 against hepatitis C virus and one against respiratory syncytial virus. This review also describes future perspectives for new antiviral therapies such as nanotechnologies, monoclonal antibodies and the CRISPR‐Cas system. These strategies are suggested as inhibitors of viral replication by various means, such as direct binding to the viral particle, blocking the infection, changes in intracellular mechanisms or viral genes, preventing replication and virion formation. We also observed that a large number of viral agents have no therapy available and the majority of those approved in the last 32 years are restricted to some groups, especially anti‐HIV. Additionally, the emergence of new viruses and strains resistant to available antivirals has necessitated the formulation of new antivirals.

Humanized Mice for Infectious and Neurodegenerative disorders

“…To gain access into the host cell, virus particles adsorb and bind to the CD4 and CCR5 or CXCR4 receptor and co-receptor proteins present on the host cell surface. Agents that block these interactions have been developed into effective drugs against HIV-1 [ 61 ]. Other antiviral drug targets include ion channel blockers or inhibitors of structural and non-structural viral proteins, reverse transcriptase enzyme, integrase, protease, and neuraminidase enzymes that catalyze polyprotein cleavage and release of mature virions.…”

“…For infectious diseases these animals can be used to study pathogen cell and tissue tropisms, replication, and virulence. Moreover, advances in disease pathogenesis, pharmacologic and vaccine research serves to mitigate the health burden of not simply infectious disease but also metabolic, cancerous, and degenerative disorders [ 1 , 2 ]. Animal models used to study each disease independent of etiology must accurately reflect the clinical and pathological features of the human condition.…”

Vaccines and Antivirals: Grand Challenges and Great Opportunities

“…Despite some limitations of neutralizing antiviral antibodies as therapeutic agents, they have potential for prevention and treatment of several viral infections (Ebola, HIV, chikungunya virus, MERS-CoV, SARS-CoV, and SARS-CoV-2) (38). The CRISPR/Cas-9 technology is being used in different antiviral strategies, including: (i) modification of viral entry receptors, (ii) knock-down of host viral factors, (iii) induction of host restrictions factors, (iv) excision and removal of viral genomes that are integrated in the host genome or persisting as episomes (39,40).…”

Mechanisms of viral persistence in the brain and therapeutic approaches

“…Despite intensive efforts, there remains a paucity of available antiviral therapies for the vast majority of viral infections. Indeed, less than 100 antiviral drugs have been approved by the United States Food and Drug Administration in the past 30 years and over half of these were developed for a single pathogen: HIV [130].…”