Cross-testing of direct-action antivirals, universal vaccines, or search for host-level antivirals: what will sooner lead to a generic capability to combat the emerging viral pandemics?

ABSTRACT

Introduction

Mitigation of future viral pandemics is an enormous technical problem, but its solution is essential for preservation of life, economic well-being, and social stability. The author examined host-level, direct action antiviral, and universal vaccine approaches while presenting a specific screening proposal.

Areas covered

The author examined the most recent biomedical literature publicly available in the databases and identified the publications supporting the principle of cross-applicability of direct-action antivirals (DAA) within similar viral families and at greater phylogenetic distances.

Expert opinion

Comparing different approaches, the author showed that the cocktails of DAAs, including parent compounds that passed Phase I trials need to be preemptively tested for all major viral families, approved, and stockpiled (or dual-use production facilities designated). The quick distribution of the pre-approved and pre-positioned antiviral cocktails (even of moderate efficiency) reduces mortality and economic damage many-fold, resulting in the trillion-scale savings in a pandemic context. This pre-positioning approach is only one in the combinatorial toolkit that needs to be included in the plan for all viral families of importance. A dedicated international public-private initiative can achieve savings in these proactive preparedness efforts, as well as to keep the focus of politicians and public on the problem.

KEYWORDS:

• Direct-action antivirals
• host-level antivirals
• universal vaccines
• pre-positioning
• emergent pathogens

Article highlights

• Viruses demonstrated hidden structural homology even between distinct families due to convergent evolution and the need to interact with analogous host structures (for example- fusion sequences to penetrate cell membranes).

• These homologies form the basis for cross-testing of direct-action antivirals and parent compounds across diverse viral species. This approach is more likely to succeed within the same family (coronaviruses, influenza, paramyxoviruses).

• The tested effective combinations will form co-formulated cocktails for treatment of humans and animals against multiple strains of the same family, including future emergent strains.

• Pre-positioning of the countermeasures – even imperfect ones – exponentially decreases the damage by the emergent pandemic.

• More than 700 direct-action and 1000 host-level compounds passed Phase I trials (for other indications) and are available for screening for these preventive roles.

• It is an obligation of civilized societies to conduct far-sighted, consistent, transparent preventive effort addressing future pandemics, where a relatively small investment forestalls enormous social disruption. This is more than relevant, considering unregulated gain-of-function research.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

A.M. solely contributed to the conception and design of the review article and interpreting the relevant literature and been involved in writing the review article or revised it for intellectual content.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The work was not funded.