Purwati: 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 [HCQ]

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

Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302 (In Vitro)

Purwati et al., An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine.., PLOS One, doi:10.1371/journal.pone.0252302 (In Vitro)

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In Vitro study of combinations of drugs showing antiviral efficacy of HCQ alone and in combination with AZ, favipiravir, and doxycycline. No high levels of cytotoxicity were observed, and authors conclude that using a combination of drugs can reduce the degree of cytotoxicity, increase antiviral activity, reduce the effect on pro-inflammatory markers, and increase anti-inflammatory response.

14 In Vitro studies support the efficacy of HCQ [Andreani, Clementi, Dang, Delandre, Faísca, Hoffmann, Liu, Ou, Purwati, Sheaff, Wang, Wang (B), Yao, Yuan].

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1. Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, https://www.sciencedirect.com/science/article/pii/S0882401020305155.

2. Clementi et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31), Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, https://www.frontiersin.org/articl..ign=ECO_FCIMB_XXXXXXXX_auto-dlvrit.

3. Dang et al., bioRxiv, doi:10.1101/2021.03.16.435741, Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, https://www.biorxiv.org/content/10.1101/2021.03.16.435741v1.

4. Delandre et al., Pharmaceuticals, doi:10.3390/ph15040445, Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, https://www.mdpi.com/1424-8247/15/4/445.

5. Faísca et al., Pharmaceutics, doi:10.3390/pharmaceutics14040877, Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, https://www.mdpi.com/1999-4923/14/4/877.

6. Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3, Chloroquine does not inhibit infection of human lung cells with SARS-CoV-2, https://www.nature.com/articles/s41586-020-2575-3.

7. Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, https://www.nature.com/articles/s41421-020-0156-0.

8. Ou et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009212 (preprint 7/22), Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, https://journals.plos.org/plospath..le?id=10.1371/journal.ppat.1009212.

9. Purwati et al., PLOS One, doi:10.1371/journal.pone.0252302, 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, https://journals.plos.org/plosone/..le?id=10.1371/journal.pone.0252302.

10. Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892, A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, https://www.biorxiv.org/content/10.1101/2020.08.02.232892v1.

11. Wang et al., Phytomedicine, doi:10.1016/j.phymed.2020.153333, Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467095/.

12. Wang (B) et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, https://www.nature.com/articles/s4..iVs8_7R1KkwOuqjRhx7psfHV6iSDRD1cM0.

13. Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), https://academic.oup.com/cid/advan..le/doi/10.1093/cid/ciaa237/5801998.

14. Yuan et al., Communications Biology, doi:10.1038/s42003-022-03841-8, Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, https://www.nature.com/articles/s42003-022-03841-8.

Purwati et al., 18 Jun 2021, peer-reviewed, 16 authors.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

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Abstract: PLOS ONE RESEARCH ARTICLE 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 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Purwati , Miatmoko A, Nasronudin , Hendrianto E, Karsari D, Dinaryanti A, et al. (2021) An in vitro study of dual drug combinations of antiviral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia. PLoS ONE 16(6): e0252302. https://doi.org/10.1371/ journal.pone.0252302 Editor: Mrinmoy Sanyal, Stanford University School of Medicine, UNITED STATES Received: October 9, 2020 Accepted: May 13, 2021 Published: June 18, 2021 Copyright: © 2021 Purwati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Funding: This study was funded by State Intelligence Agency (BIN) of Republic of Indonesia. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Purwati ID1,2,3*, Andang Miatmoko1,4, Nasronudin5, Eryk Hendrianto1, Deya Karsari1, Aristika Dinaryanti1, Nora Ertanti1, Igo Syaiful Ihsan1, Disca Sandyakala Purnama1, Tri Pudy Asmarawati5, Erika Marfiani5, Yulistiani4,5, Alfian Nur Rosyid5, Prastuti Asta Wulaningrum5, Herley Windo Setiawan5, Imam Siswanto6, Ni Nyoman Tri Puspaningsih7 1 Stem Cell Research and Development Center, Institute of Tropical Disease, Universitas Airlangga, Mulyorejo, Surabaya, Indonesia, 2 Faculty of Vocations, Universitas Airlangga, Gubeng, Surabaya, Indonesia, 3 Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan, 4 Faculty of Pharmacy, Universitas Airlangga, Mulyorejo, Surabaya, Indonesia, 5 Rumah Sakit Umum dan Rumah Sakit Khusus Infeksi, Universitas Airlangga, Mulyorejo, Surabaya, Indonesia, 6 Bioinformatic Laboratory, UCoE Research Center for Bio-Molecule Engineering Universitas Airlangga, Surabaya, Indonesia, 7 Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia * purwati@fk.unair.ac.id Abstract 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; LopinavirRitonavir (LOPIRITO)-Clarithromycin (CLA), LOPIRITO-Azithromycin (AZI), LOPIRITODoxycycline (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 (CC50) 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 IC50 24, 48, and 72 hours after viral inoculation was subsequently determined...

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