The current progress in the use of boron as a platform for novel antiviral drug design

ABSTRACT

Introduction

Boron has attracted extensive interest due to several FDA-approved boron-containing drugs and other pharmacological agents in clinical trials. As a semimetal, it has peculiar biochemical characteristics which could be utilized in designing novel drugs against drug-resistant viruses. Emerging and reemerging viral pandemics are major threats to human health. Accordingly, we aim to comprehensively review the current status of antiviral boron-containing compounds.

Areas covered

This review focuses on the utilization of boron to design molecules against viruses from two perspectives: (i) single boron atom-containing compounds acting on miscellaneous viral targets and (ii) boron clusters. The peculiar properties of antiviral boron-containing compounds and their diverse binding modes with viral targets are described in detail in this review.

Expert opinion

Compounds bearing boronic acid can interact with viral targets by forming covalent or robust hydrogen bonds. This feature is valuable for combating resistant viruses. Furthermore, boron clusters can form dihydrogen bonds and bear features such as three-dimensional aromaticity, hydrophobicity, and biological stability. All these features demonstrated boron as a probable essential element with immense potential for drug design.

KEYWORDS:

• Antiviral agents
• boron clusters
• drug design
• medicinal chemistry
• single boron atom-containing compounds

Article highlights

• The peculiar properties of antiviral boron-containing compounds and their diverse binding modes with viral targets are described in detail with the hope of boosting the utilization of boron as a platform for novel antiviral drug design.

• The ability of boronic acid to form covalent or robust hydrogen bonds is valuable when designing antiviral agents.

• Boronic acid derivatives with potent inhibitory activity against SARS-CoV 3CL^pro can also be utilized to discover novel anti-SARS-CoV-2 inhibitors.

• Boron clusters cannot form conventional hydrogen bonds; instead, they form dihydrogen bonds that could interact with biological targets in a peculiar manner.

Declaration of Competing Interest

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.

Additional information

Funding

Authors of this paper received financial support from the Natural Science Foundation of China (grant numbers 82173677 and 81974507), Science Foundation for Outstanding Young Scholars of Shandong Province (ZR2020JQ31), Foreign Cultural and Educational Experts Project (GXL20200015001), Qilu Young Scholars Program of Shandong University, and the Taishan Scholar Program at Shandong Province.