Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: Peak plasma concentration of Lopinavir/Ritonavir (LOPIRITO), Azithromycin (AZI), Clarithromycin (CLA), Doxycycline (DOXY), Hydroxychloroquine (HCQ), and Favipiravir (FAVI) after a single oral administration of the drug.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Concentration Assay

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The cytotoxicities of Hydroxychloroquine (HCQ) and Azithromycin (AZI) as a single drug (left) and dual drug combination in constant and non-constant ratios (right) analysed by using CompuSyn Software (n = 3). At non-constant ratios of HCQ + AZI 50 μg/mL, AZI was added at a concentration of 50 μg/mL to each increased levels of HCQ i.e. 0.2, 2, 10, 100, and 400 μg/mL. On the other hand, HCQ was then added at a concentration of 6 μg/mL to each increased levels of AZI i.e. 0.2, 2, 10, 100, and 400 μg/mL to produce HCQ 6 μg/mL + AZI.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Software, Concentration Assay

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The cytotoxicities of Hydroxychloroquine (HCQ) and Doxycycline (DOXY) as a single drug (left) and dual drug combination in constant and non-constant ratios (right) analysed by using CompuSyn Software (n = 3). At non-constant ratios of HCQ + DOXY 2 μg/mL, DOXY was added at a concentration of 2 μg/mL to each increased levels of HCQ i.e. 0.2, 2, 10, 100, and 400 μg/mL. On the other hand, HCQ was then added at a concentration of 6 μg/mL to each increased levels of DOXY i.e. 0.2, 2, 10, 100, and 400 μg/mL to produce HCQ 6 μg/mL + DOXY.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Software, Concentration Assay

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The cytotoxicities of Hydroxychloroquine (HCQ) and Favipiravir (FAVI) as a single drug (left) and dual drug combination in constant and non-constant ratios (right) analysed by using CompuSyn Software (n = 3). At non-constant ratios of HCQ 6 μg/mL + FAVI, HCQ was added at a concentration of 66 μg/mL to each increased levels of FAVI i.e. 0.2, 2, 10, 100, and 400 μg/mL. On the other hand, FAVI was then added at a concentration of 66 μg/mL to each increased levels of HCQ i.e. 0.2, 2, 10, 100, and 400 μg/mL to produce HCQ + FAVI 66 μg/mL.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Software, Concentration Assay

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The cytotoxicities of Hydroxychloroquine (HCQ) and Lopinavir-Ritonavir (LOPIRITO) as a single drug (left) and dual drug combination in constant and non-constant ratios (right) analysed by using CompuSyn Software (n = 3). At non-constant ratios of HCQ + LOPIRITO 8 μg/mL, LOPIRITO was added at a concentration of 8 μg/mL to each increased levels of HCQ i.e. 0.2, 2, 10, 100, and 400 μg/mL. On the other hand, HCQ was then added at a concentration of 6 μg/mL to each increased levels of LOPIRITO i.e. 0.2, 2, 10, 100, and 400 μg/mL to produce HCQ 6 μg/mL + LOPIRITO.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Software, Concentration Assay

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The summary of antiviral activity (IC 50 ) of single and combination drugs against Vero cells infected with SARS-CoV-2 at an multiplicity of infection (MoI) value of 0.04.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Activity Assay, Infection

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The efficacy (IC 50 ) evaluation of Lopinavir-Ritonavir (LOPIRITO), Favipiravir (FAVI), Azithromycin (AZI), Clarithromycin (CLA), Doxycycline (DOXY), and Hydroxychloroquine (HCQ) as a single drug in Vero cells infected with SARS-CoV-2 virus isolates for 24 hours (A), 48 hours (B), and 72 hours (C) analysed using CompuSyn Software at a multiplicity of infection (MoI) value of 0.04.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Infection, Software

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The efficacy (IC 50 ) evaluation of dual combination of Lopinavir-Ritonavir (LOPIRITO), Azithromycin (AZI), Doxycycline (DOXY), Favipiravir (FAVI), Clarithromycin (CLA), and Hydroxychloroquine (HCQ) as a single drug in Vero cells infected with SARS-CoV-2 virus isolates for 24 hours (A), 48 hours (B), and 72 hours (C) analysed using CompuSyn Software at a multiplicity of infection (MoI) value of 0.04.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Infection, Software

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The concentration of single and combination drugs (at a mass ratio) that produced an undetected virus copy number in the in vitro antiviral study against Vero cells infected with SARS-CoV-2 at a multiplicity of infection (MoI) value of 0.04 at 24, 48, and/or 72 hours’ incubation.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Concentration Assay, Produced, In Vitro, Infection, Incubation

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The summary of the cytokine levels of Vero cells infected with SARS-CoV-2 isolates an multiplicity of infection (MoI) value of 0.04 at 24, 48, and 72 hours incubated with single and drug combinations. The data were in duplicates.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Infection, Incubation

Journal: PLoS ONE

Article Title: 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

doi: 10.1371/journal.pone.0252302

Figure Lengend Snippet: The docking scores of potential SARS-CoV-2 main protease inhibitor drug.

Article Snippet: Lopinavir-Ritonavir (LOPIRITO) was produced by Abbott Laboratories (Aluvia®, Chicago, USA); Favipiravir (FAVI) by Toyama Chemical (Fujifilm Group) (Avigan®, Japan); Azithromycin (AZI) tablets by Gentec Pharmaceutical Group (Spain); Clarithromycin (CLA) by Ind Swift Laboratories Limited (India); Doxycycline (DOXY) by Genero Pharmaceuticals (Doxicor®, Indonesia); Hydroxychloroquine (HCQ) by Imedco Djaja (Hyloquin®, Indonesia); and dimethyl sulfoxide by Sigma Aldrich (Singapore).

Techniques: Protease Inhibitor, Molecular Weight

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: In vivo impact of azithromycin and hydroxychloroquine on the IL-6R transcript and proteins levels. ( a ) mRNA levels of IL6R in untreated guinea pig hearts (control) and in guinea pigs treated with AZM (1) and HCQ (2) for 30 min. ( b ) Densitometric analysis and ( c ) the corresponding western blot for IL6Rα proteins untreated guinea pig heart lysate (control) and guinea pigs treated with AZM (1) and HCQ (2) for 30 min. The blots were probed with a monoclonal antibody for IL6Rα (Anti IL6Rα—H7 Santa Cruz). The band at 80 kDa represents IL6Rα. GAPDH indicates internal control. Each experiment was performed in triplicates from 4 guinea pigs (2 controls, lanes 1 & 2 and 2 treated with AZM + HCQ, lanes 3 & 4).

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: In Vivo, Control, Western Blot

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: In-vivo impact of tocilizumab, interleukin-6, azithromycin and hydroxychloroquine on the electrocardiogram of guinea pigs ( a ) ECG of a guinea pig before, ( b ) after administration of TCZ (10 mg/kg) alone, ( c ) TCZ + IL-6(184 μg/kg), ( d ) TCZ + IL-6 + AZM(1) + HCQ(0.5), ( e ) TCZ + IL-6 + AZM(1) + HC(1) and ( f ) TCZ + IL-6 + AZM (1) + HCQ(2). Comparison of individual data points for heart rate (HR), PR, QRS and QTc between baseline and different interventions is illustrated in panels ( g–j ). AZM(1) = 38.2 mg/kg; HCQ (0.5) = 22.9 mg/kg; HCQ(1) = 45.8 mg/kg; HCQ(2) = 91.6 mg/kg. p values shown are in comparison to basal conditions.

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: In Vivo, Comparison

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: In-vivo impact of interleukin-6, azithromycin and hydroxychloroquine on the electrocardiogram of guinea pigs. ( a ) ECG of a guinea pig before, ( b ) after administration of IL-6(184 μg/kg) alone, ( c ) IL-6 + AZM(1) + HCQ(0.5), ( d ) IL-6 + AZM(1) + HC(1) and ( e ) IL-6 + AZM (1) + HCQ(2). Comparison of individual data points for heart rate (HR), PR, QRS and QTc between baseline and different interventions is illustrated in panels ( f–i) using paired t -test versus basal group and one-way repeated measures analysis of variance for multiple comparisons among the drug interventions. Heart rate ( j ), PR ( k ), QRS ( l ) and QTc ( m ) data from two groups of guinea pigs, one (n = 6) injected with AZM (1) and HCQ (0.5) and the other (n = 6) injected with IL-6 (184 μg/kg) + AZM (1) + HCQ (0.5). AZM (1) = 38.2 mg/kg; HCQ(0.5) = 22.9 mg/kg; HCQ(1) = 45.8 mg/kg; HCQ(2) = 91.6 mg/kg. p values shown are in comparison to basal conditions.

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: In Vivo, Comparison, Injection

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: In-vitro impact of interleukin-6, azithromycin and hydroxychloroquine on the electrogram of Langendorff perfused guinea pig hearts. Electrograms of an isolated guinea pig heart before ( a ) and ( b ) after perfusions of IL-6 (200 μg/L) alone for 40 min, ( c ) IL-6 + AZM(1) + HCQ(0.5), ( d ) IL-6 + AZM(1) + HCQ(1) and ( e ) IL-6 + AZM (1) + HCQ (2). The comparison of individual data points for heart rate (HR), PR, QRS and QTc between baseline and the different interventions is illustrated in panels ( f–i) using paired t-test. Heart rate ( j ), PR ( k ), QRS ( l ) and QTc ( m ) data from two groups of guinea pigs, one (n = 5) perfused with AZM(1) and HCQ(0.5) and the other (n = 5) perfused with IL-6(200 µg/L) + AZM(1) + HCQ(0.5). AZM(1) = 41.5 mg/L; HCQ(0.5) = 24.9 mg/L. AZM(1) = 41.5 mg/L; HCQ(0.5) = 24.9 mg/L; HCQ(1) = 49.8 mg/L; HCQ(2) = 99.6 mg/L. Paired t-test was used to compare interventions to baseline. (*) indicates p < 0.05.

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: In Vitro, Isolation, Comparison

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: Impact of interleukin-6, azithromycin and hydroxychloroquine on action potential and key ion channels in guinea pig ventricular myocytes. Action potentials ( a ) and ion currents, I CaL ( b ), I Na ( c ) and I Kr ( g–k ) recorded from control myocytes (black traces) and from another group of myocytes preincubated with IL-6 for 40 min (red traces), IL-6(200 µg/L) + AZM (1) + HCQ (0.1) (green traces), IL-6 + AZM (1) + HCQ(0.5) (pink traces) and IL-6 + AZM(1) + HCQ(1) (dark red traces). The comparison of individual data points for APD 90 ( d ) and current densities for I CaL ( e ), I Na ( f ) and I Kr ( l ) during control and after different interventions is presented. HCQ(0.1) = 5.0 mg/L; HCQ(0.5) = 24.9 mg/L; HCQ(1) = 49.8 mg/L; AZM(1) = 41.5 mg/L. Unpaired t-test was used between the control group and the group treated with IL-6 + AZM + HCQ. p values shown are comparison to basal conditions.

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: Control, Comparison

Journal: Scientific Reports

Article Title: Arrhythmogenic mechanisms of interleukin-6 combination with hydroxychloroquine and azithromycin in inflammatory diseases

doi: 10.1038/s41598-022-04852-5

Figure Lengend Snippet: Impact of azithromycin and hydroxychloroquine with and without interleukin-6 on action potential and key ion channels in guinea pig ventricular myocytes. APD 90 ( a ), AP amplitude (APA, b ), I CaL ( c ) I Na ( d ) and I Kr ( e ) data from two groups of guinea pig myocytes before (basal) and after administrations of AZM(1) + HCQ(0.1); and the other control group without IL-6 and the treated group with IL-6 (200 μg/L), AZM(1) and HQC(0.1). AZM(1) = 41.5 mg/L; HCQ(0.5) = 24.9 mg/L. Paired t-test was used within the same group before (basal) and with (AZM + HCQ). Unpaired t-test was used between control group and the group treated with IL-6 + AZM + HCQ. p values shown are comparison to basal conditions.

Article Snippet: Hydroxychloroquine Sulfate (HCQ) was purchased from GLPBIO (USA, batch number: GC125441).

Techniques: Control, Comparison