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Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.

ABSTRACT: While the coronavirus disease 2019 (COVID-19) pandemic advances, the scientific community continues to struggle in the search for treatments. Several improvements have been made, including discovery of the clinical efficacy of chloroquine (CQ) in patients with COVID-19, but effective treatment protocols remain elusive. In the search for novel treatment options, many scientists have used the in-silico approach to identify compounds that could interfere with the key molecules involved in entrance, replication or dissemination of severe acute respiratory syndrome coronavirus-2. However, most of the identified molecules are not available as pharmacological agents at present, and assessment of their safety and efficacy could take many months. This review took a different approach based on the proposed pharmacodynamic model of CQ in COVID-19. The main mechanism of action responsible for the favourable outcome of patients with COVID-19 treated with CQ seems to be related to a pH-modulation-mediated effect on endolysosomal trafficking, a characteristic of chemical compounds often called 'lysosomotropic agents' because of the physico-chemical properties that enable them to diffuse passively through the endosomal membrane and undergo protonation-based trapping in the lumen of the acidic vesicles. This review discusses lysosomotropic and lysosome targeting drugs that are already in clinical use and are characterized by good safety profiles, low cost and wide availability. Some of these drugs -particularly azithromycin and other macrolides, indomethacin and some other non-steroidal anti-inflammatory drugs, proton pump inhibitors and fluoxetine - could provide additional therapeutic benefits in addition to the potential antiviral effect that is still to be confirmed by well-controlled clinical trials. As some of these drugs have probably been used empirically in the treatment of COVID-19, it is hoped that colleagues worldwide will publish patient data to enable evaluation of the potential efficacy of these agents in the clinical context, and rapid implementation in therapeutic protocols if they are shown to have a beneficial effect on clinical outcome.

SUBMITTER: Homolak J

PROVIDER: S-EPMC7275137 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.

Homolak J J Kodvanj I I

International journal of antimicrobial agents 20200606 2

While the coronavirus disease 2019 (COVID-19) pandemic advances, the scientific community continues to struggle in the search for treatments. Several improvements have been made, including discovery of the clinical efficacy of chloroquine (CQ) in patients with COVID-19, but effective treatment protocols remain elusive. In the search for novel treatment options, many scientists have used the in-silico approach to identify compounds that could interfere with the key molecules involved in entrance, ...[more]

PMID: 32522674

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Project description:Coronaviruses are pleomorphic, enveloped, or spherical viruses, which have a size ranging from 80 to 120 nm. These viruses act on receptors that cause the triggering of fusion. Coronaviruses were first described after cultivation from patients with common colds by Tyrell and Bynoe in 1966. There are various subtypes of coronavirus, 7 out of these can cause infection in human beings. The Alpha subtype is responsible for mild infection showing symptoms or infection without any prevailing symptoms. On the other hand, the beta subtype is responsible for very serious diseases leading to fatality. The lineage of this novel SARS-CoV-2 falls under the beta lineage of the beta coronavirus which has been observed to have a relation to the MERS and SARS coronavirus. In the Huanan market selling seafood, the transition of this novel virus in humans from animals has occurred. It has the potential to be the cause of widespread fatality amongst the people of the globe. On August 16, 2020, the World Health Organisation had reported 2,1294,845 cases which are confirmed to date out of which 413,372 deaths have occurred. Currently, no targeted antiviral vaccines or drugs to fight against COVID-19 infection have been approved for use in humans. This pandemic is fast emerging and drug repurposing is the only ray of hope which can ensure quick availability. Vaccine development is progressing each day with various platforms such as DNA, Live Attenuated Virus, Non-Replicating Viral Vector, Protein Subunit, and RNA, being utilized for the development. COVID-19 attacks the immune system of the host & this can result in a cytokine storm. As a result, various herbal agents both acting as antivirals and immunomodulatory can also be used. Convalescent Plasma Therapy and Mesenchymal Stem Cell therapy are also being explored as a plausible therapeutic. There remains a considerable unmet need for therapeutics to be addressed. The development and availability of accessible and efficient therapy are essential for the treatment of patients. This review discusses the epidemiology, pathogenesis, the tale of origin, and transmission of COVID-19 or Sars-Cov2 virus and gives evidence of potential therapeutic agents that can be explored to cast away this pandemic.

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Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.

Publications

Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.

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