dc.contributor.author | Leung, Anthony K. L. | |
dc.contributor.author | Griffin, Diane E. | |
dc.contributor.author | Bosch, Jürgen | |
dc.contributor.author | Fehr, Anthony R. | |
dc.date.accessioned | 2022-02-08T15:17:49Z | |
dc.date.available | 2022-02-08T15:17:49Z | |
dc.date.issued | 2022-01-14 | |
dc.identifier.citation | Leung, A.K.L.; Griffin, D.E.; Bosch, J.; Fehr, A.R. The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses. Pathogens 2022, 11, 94. https://doi.org/10.3390/pathogens11010094 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32499 | |
dc.description.abstract | Emerging and re-emerging viral diseases pose continuous public health threats, and effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, and prevention with vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide effective treatments. This lack of preparedness has been due, in large part, to a lack of investment in developing a diverse portfolio of antiviral agents, particularly those ready to combat viruses of pandemic potential. Here, we focus on a drug target called macrodomain that is critical for the replication and pathogenesis of alphaviruses and coronaviruses. Some mutations in alphavirus and coronaviral macrodomains are not tolerated for virus replication. In addition, the coronavirus macrodomain suppresses host interferon responses. Therefore, macrodomain inhibitors have the potential to block virus replication and restore the host’s protective interferon response. Viral macrodomains offer an attractive antiviral target for developing direct acting antivirals because they are highly conserved and have a structurally well-defined (druggable) binding pocket. Given that this target is distinct from the existing RNA polymerase and protease targets, a macrodomain inhibitor may complement current approaches, pre-empt the threat of resistance and offer opportunities to develop combination therapies for combating COVID-19 and future viral threats. | en_US |
dc.publisher | MDPI | en_US |
dc.rights | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Coronavirus | en_US |
dc.subject | Alphavirus | en_US |
dc.subject | SARS-CoV-2 | en_US |
dc.subject | Macrodomain | en_US |
dc.subject | ADP-ribosylation | en_US |
dc.subject | ADP-ribosylhydrolase | en_US |
dc.subject | Therapeutics | en_US |
dc.title | The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Fehr, Anthony R. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.3390/pathogens11010094 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0001-5569-4036 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0001-6643-2429 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0002-2624-4105 | en_US |
dc.identifier.orcid | https://orcid.org/ 0000-0003-1560-1573 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC8780475 | en_US |
dc.rights.accessrights | openAccess | en_US |