[HTML][HTML] Broad-spectrum antiviral agents: a crucial pandemic tool

A Adalja, T Inglesby - Expert review of Anti-infective Therapy, 2019 - Taylor & Francis
A Adalja, T Inglesby
Expert review of Anti-infective Therapy, 2019Taylor & Francis
Among the myriad infectious disease threats humans face from bacteria, prions, parasites,
protozoa, fungi, ectoparasites, and viruses, it is viral infections that arguably constitute the
biggest pandemic threat in the modern era. The replication rates and transmissibility of
viruses are two major factors that underlie this threat. However, at least one additional factor
plays an essential role: the lack of Lbroad-spectrumL antiviral agents. Indeed, while bacteria
can still cause substantial epidemics in parts of the world where access to clean water …
Among the myriad infectious disease threats humans face from bacteria, prions, parasites, protozoa, fungi, ectoparasites, and viruses, it is viral infections that arguably constitute the biggest pandemic threat in the modern era. The replication rates and transmissibility of viruses are two major factors that underlie this threat. However, at least one additional factor plays an essential role: the lack of Lbroad-spectrumL antiviral agents. Indeed, while bacteria can still cause substantial epidemics in parts of the world where access to clean water and/or antimicrobials is limited, the pandemic threats posed by bacteria, such as from the plague-causing Yersinia pestis, has been substantially diminished in the antibiotic era [1]. For viruses that pose epidemic risks, on the other hand, current therapeutic options are more limited. Viruses, by their obligate parasitical nature, must use host cell machinery for many functions. Thus, antiviral strategies must be directed at the virus specifically with care to avoid interfering with host cellular function. As such, the number of clear targets per virus may be limited. By contrast, bacterial protein synthesis, for example, occurs via ribosomes that belong to the bacteria and are disparate enough from human ribosomes in identity that specific antibiotics can be deployed to target only bacterial protein synthesis. This unique feature of viruses, which derives from their very nature, serves to delimit antiviral therapies in a manner not applicable to antibacterial therapies. Additionally, other characteristics of viruses serve as obstacles to broad-spectrum antiviral agents. These include differences between RNA and DNA viruses, vastly different virally encoded proteins across viral families, single or double strand genomic structure, cytoplasmic or nuclear replications cycles, and degree of reliance on host proteins. The existing armamentarium of antiviral drugs is rapidly expanding and now covers several viral families. However, very few existing antiviral agents have spectrums of activity that even slightly measure up to the spectrum of penicillin or sulfa, the first anti-bacterial agents discovered.
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