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Title:

Broad-Spectrum Antiviral Agents: A Crucial Pandemic Tool

Authors:
Amesh Adalja, Thomas Inglesby
Date posted:
June 24, 2019
Publication type:
Article
Publication:

Expert Review of Anti-infective Therapy

Publisher:
Taylor & Francis
DOI:
10.1080/14787210.2019.1635009
Availability:
Available on publisher's website
See also:

Full article on publisher's website: HTML • PDF

Introduction:

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 ‘broad-spectrum’ 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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