Drugs, host proteins and viral proteins: how their promiscuities shape antiviral design

Abstract

The reciprocal nature of drug specificity and target specificity implies that the same is true for their respective promiscuities. Protein promiscuity has two broadly different types of footprint in drug design. The first is relaxed specificity of binding sites for substrates, inhibitors, effectors or cofactors. The second involves protein–protein interactions of regulatory processes such as signal transduction and transcription, and here protein intrinsic disorder plays an important role. Both viruses and host cells exploit intrinsic disorder for their survival, as do the design and discovery programs for antivirals. Drug action, strictly speaking, always relies upon promiscuous activity, with drug promiscuity enlarging its scope. Drug repurposing searches for additional promiscuity on the part of both the drug and the target in the host. Understanding the subtle nuances of these promiscuities is critical in the design of novel and more effective antivirals.

White & grey biotechnologies for shaping a sustainable future

“…These unusual applications mostly become possible because of what is called enzyme promiscuity. 26,[83][84][85][86][87][88][89][90] Substrate promiscuity refers to what has been known as the broad specicity of enzymes. A lipase may hydrolyse fats and oils made up of different fatty acids.…”

“…We have over-focussed on enzyme specicity even though so much has been possible in biotechnology because of non-specicity. 26,[83][84][85][86][87][88][89][90][91][92]97,98 With a change in mindset, more innovations would be possible. A good example of this is the use of inexpensive hydrolases such as amylase in bioremediation of alkanes.…”

Pre-Molten, Wet, and Dry Molten Globules <i>En Route</i> to the Functional State of Proteins

“…Do they play a role in immune responses [293]? What are the various ways we can use them in applied biocatalysis or drug delivery designs [294][295][296][297][298][299][300]? We already know that partially unfolded states of some proteins are precursors to aggregation, and many diseases originate from aggregation via intrinsic disorder [301][302][303][304][305][306][307][308][309][310].…”

What does Our Experience of COVID-19 Teach Us?

“…While the development of vaccines may take years, drug repurposing can offer disease mitigation much quicker. Drug repurposing studies present a promising and accelerated strategy to develop therapy because these drugs have known safety profiles (Gupta & Roy, 2021). For example, in case of COVID-19, many research publications reported sets of experimentally validated drugs as potential COVID-19 therapies within a very short period of time.…”