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. 2021 Dec;36(1):1056-1060.
doi: 10.1080/14756366.2021.1927007.

Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms

Claudiu T Supuran  1 , Alessio Nocentini  1 , Elena Yakubova  2 , Nikolay Savchuk  2   3 , Stanislav Kalinin  4 , Mikhail Krasavin  4
Affiliations

Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms

Claudiu T Supuran et al. J Enzyme Inhib Med Chem. 2021 Dec.

Abstract

The non-nucleoside reverse transcriptase inhibitor VM1500A is approved for the treatment of HIV/AIDS in its N-acyl sulphonamide prodrug form elsulfavirine (Elpida®). Biochemical profiling against twelve human carbonic anhydrase (CA, EC 4.2.1.1) isoforms showed that while elsulfavirine was a weak inhibitor of all isoforms, VM1500A potently and selectively inhibited human (h) hCA VII isoform, a proven target for the therapy of neuropathic pain. The latter is a common neurologic complication of HIV infection and we hypothesise that by using Elpida® in patients may help alleviate this debilitating symptom.

Keywords: N-acyl sulphonamide prodrug; Non-nucleoside reverse transcriptase inhibitor; elsulfavirine; human carbonic anhydrase; isoform selectivity; neuropathic pain.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Elsufavirine (Elpida) and VM1500A.
Figure 2.
Figure 2.
Schematic representation of a sulphonamide-based CAI bound in the active site of CA.
Figure 3.
Figure 3.
Predicted binding pose of VM1500A (green) within the active site of hCA VII.
See this image and copyright information in PMC

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