An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia

A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed pa...

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Vydané v:	PloS one Ročník 16; číslo 6; s. e0252302
Hlavní autori:	Purwati, Miatmoko, Andang, Nasronudin, Hendrianto, Eryk, Karsari, Deya, Dinaryanti, Aristika, Ertanti, Nora, Ihsan, Igo Syaiful, Purnama, Disca Sandyakala, Asmarawati, Tri Pudy, Marfiani, Erika, Yulistiani, Rosyid, Alfian Nur, Wulaningrum, Prastuti Asta, Setiawan, Herley Windo, Siswanto, Imam, Tri Puspaningsih, Ni Nyoman
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	San Francisco Public Library of Science 18.06.2021 Public Library of Science (PLoS)
Predmet:	Anti-inflammatory agents Anti-virus software Antibiotics Antiviral agents Antiviral drugs Antivirus programs Astrocytes Azithromycin Biology and Life Sciences Biomolecules Biotechnology Cell lines Chloroquine Clarithromycin Complications and side effects Computer and Information Sciences Computer programs Coronaviruses COVID-19 Data analysis Drafting software Drug therapy, Combination Editing Engineering and Technology Hospital patients Hydroxychloroquine Immunomodulators Inflammation Interferon Laboratories Lopinavir Medicine and Health Sciences Mesenchymal stem cells Methodology Patient outcomes Pneumonia R&D Research & development Research and Analysis Methods Research facilities Ribavirin Ritonavir Science and technology Severe acute respiratory syndrome coronavirus 2 Software Stem cells Tropical diseases Vector-borne diseases Viral diseases Viral infections Viruses Visualization α-Interferon Indonesia United States > US China
ISSN:	1932-6203, 1932-6203
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Popis
Shrnutí:	A potent therapy for the infectious coronavirus disease COVID-19 is urgently required with, at the time of writing, research in this area still ongoing. This study aims to evaluate the in vitro anti-viral activities of combinations of certain commercially available drugs that have recently formed part of COVID-19 therapy. Dual combinatory drugs, namely; Lopinavir-Ritonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITO-Doxycycline (DOXY), Hydroxychloroquine (HCQ)-AZI, HCQ-DOXY, Favipiravir (FAVI)-AZI, HCQ-FAVI, and HCQ-LOPIRITO, were prepared. These drugs were mixed at specific ratios and evaluated for their safe use based on the cytotoxicity concentration (CC 50 ) values of human umbilical cord mesenchymal stem cells. The anti-viral efficacy of these combinations in relation to Vero cells infected with SARS-CoV-2 virus isolated from a patient in Universitas Airlangga hospital, Surabaya, Indonesia and evaluated for IC 50 24, 48, and 72 hours after viral inoculation was subsequently determined. Observation of the viral load in qRT-PCR was undertaken, the results of which indicated the absence of high levels of cytotoxicity in any samples and that dual combinatory drugs produced lower cytotoxicity than single drugs. In addition, these combinations demonstrated considerable effectiveness in reducing the copy number of the virus at 48 and 72 hours, while even at 24 hours, post-drug incubation resulted in low IC 50 values. Most combination drugs reduced pro-inflammatory markers, i.e. IL-6 and TNF-α, while increasing the anti-inflammatory response of IL-10. According to these results, the descending order of effective dual combinatory drugs is one of LOPIRITO-AZI>LOPIRITO-DOXY>HCQ-AZI>HCQ-FAVI>LOPIRITO-CLA>HCQ-DOX. It can be suggested that dual combinatory drugs, e.g. LOPIRITO-AZI, can potentially be used in the treatment of COVID-19 infectious diseases.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0252302