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Published on: May 24, 2020
Viroporins of Mpox Virus
Kingshuk Basu1, Miriam Krugliak1, Isaiah T Arkin1
1Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
Abstract:
Mpox or monkeypox virus (MPXV) belongs to the subclass of Poxviridae and has emerged recently as a global threat. With a limited number of anti-viral drugs available for this new virus species, it is challenging to thwart the illness it begets. Therefore, characterizing new drug targets in the virus may prove advantageous to curbing the disease. Since channels as a family are excellent drug targets, we have sought to identify viral ion channels for this virus, which are instrumental in formulating channel-blocking anti-viral drugs. Bioinformatics analyses yielded eight transmembranous proteins smaller or equal to 100 amino acids in length. Subsequently, three independent bacteria-based assays have pointed to five of the eight proteins that exhibit ion channel activity. Finally, we propose a tentative structure of four ion channels from their primary amino acid sequences, employing AlphaFold2 and molecular dynamic simulation methods. These results may represent the first steps in characterizing MPXV viroporins en route to developing blockers that inhibit their function.
Insights
Researchers identified potential drug targets in the mpox virus (MPXV). Five viral proteins show ion channel activity, offering new avenues for developing antiviral drugs to combat this emerging global threat.
Area of Science:
- Virology
- Molecular Biology
- Biophysics
Background:
- Mpox virus (MPXV), a Poxviridae family member, poses a growing global health concern.
- Limited antiviral therapies exist, necessitating the identification of novel therapeutic targets.
- Viral ion channels are recognized as promising targets for antiviral drug development.
Purpose of the Study:
- To identify and characterize potential viral ion channels in MPXV.
- To explore these channels as targets for novel antiviral drug discovery.
- To lay the groundwork for developing channel-blocking therapeutics against MPXV.
Main Methods:
- Bioinformatic analysis to identify potential transmembrane proteins.
- Bacteria-based assays to confirm ion channel activity.
- AlphaFold2 and molecular dynamics simulations for structural prediction.
Main Results:
- Eight transmembrane proteins of MPXV, ≤100 amino acids, were identified.
- Five of these proteins demonstrated ion channel activity in experimental assays.
- Tentative structures for four MPXV ion channels were proposed using computational methods.
Conclusions:
- The study identifies five MPXV proteins with ion channel activity, termed viroporins.
- These viroporins represent potential targets for developing new antiviral drugs.
- The findings offer a foundational step towards creating MPXV channel blockers.
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