Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3122
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Introduction: Treatment of influenza A virus infections is currently limited to few direct acting antiviral substances. Repurposing other established pharmaceuticals as antivirals could aid in improving treatment options.
Methods: This study investigates the antiviral properties of ProcCluster and procaine hydrochloride, two derivatives of the local anesthetic procaine, in influenza A virus infection of A549, Calu-3 and MDCK cells.
Results: Both substances inhibit replication in all three of these cell lines in multi-cycle experiments. However, cell line-dependent differences in the effects of the substances on viral RNA replication and subsequent protein synthesis, as well as release of progeny viruses in single-cycle experiments can be observed. Both ProcCluster and procaine hydrochloride delay endosome fusion of the virus early in the replication cycle, possibly due to the alkaline nature of the active component procaine. In A549 and Calu-3 cells an additional effect of the substances can be observed at late stages in the first replication cycle. Interestingly, this effect is absent in MDCK cells. We demonstrate that ProcCluster and procaine hydrochloride inhibit phospholipase A (PLA) enzymes from A549 but not MDCK cells and confirm that specific inhibition of calcium independent PLA but not cytosolic PLA has antiviral effects.
Discussion: We show that ProcCluster and procaine hydrochloride inhibit influenza A virus infection at several stages of the replication cycle and have potential as antiviral substances.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350405 | PMC |
http://dx.doi.org/10.3389/fmicb.2024.1422651 | DOI Listing |
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