|
Antiviral activity against Ebolavirus Kikwit infected in human HeLa cells assessed as reduction in viral glycoprotein levels preincubated with cells for 2 hrs followed by viral infection measured after 48 hrs by immunostaining based assay
|
Ebolavirus
|
100.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
Year : 2017
Volume : 60
Issue : 5
First Page : 1648
Last Page : 1661
Authors : Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
Abstract : The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
|
Antiviral activity against GFP-fused Ebolavirus infected in TERT-immortalized HMVEC assessed as reduction in viral replication preincubated with cells followed by viral infection measured after 3 to 4 days by fluorescence assay
|
Ebolavirus
|
53.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
Year : 2017
Volume : 60
Issue : 5
First Page : 1648
Last Page : 1661
Authors : Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
Abstract : The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
|
Antiviral activity against Respiratory syncytial virus A2 infected in human Hep2 cells assessed as reduction of virus-induced cytopathic effect after 4 days by Cell-Titer Glo assay
|
Human respiratory syncytial virus A2
|
15.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
Year : 2017
Volume : 60
Issue : 5
First Page : 1648
Last Page : 1661
Authors : Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
Abstract : The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
|
Antiviral activity against Hepatitis C virus genotype 1b infected in human HuH7 cells preincubated with cells for 3 days followed by viral infection by luciferase assay
|
Hepatitis C virus subtype 1b
|
57.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
Year : 2017
Volume : 60
Issue : 5
First Page : 1648
Last Page : 1661
Authors : Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
Abstract : The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
|
Antiviral activity against Ebolavirus Kikwit infected in human macrophages preincubated with cells for 2 hrs followed by viral infection measured after 48 hrs
|
Ebolavirus
|
86.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
Year : 2017
Volume : 60
Issue : 5
First Page : 1648
Last Page : 1661
Authors : Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B, Wang Q, Wolfe L, Jordan R, Soloveva V, Knox J, Perry J, Perron M, Stray KM, Barauskas O, Feng JY, Xu Y, Lee G, Rheingold AL, Ray AS, Bannister R, Strickley R, Swaminathan S, Lee WA, Bavari S, Cihlar T, Lo MK, Warren TK, Mackman RL.
Abstract : The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
|
Antiviral activity against Ebolavirus infected in human primary macrophages after 48 hrs by immuno-staining assay
|
Ebolavirus
|
86.0
nM
|
|
Journal : J Med Chem
Title : The ProTide Prodrug Technology: From the Concept to the Clinic.
Year : 2018
Volume : 61
Issue : 6
First Page : 2211
Last Page : 2226
Authors : Mehellou Y, Rattan HS, Balzarini J.
Abstract : The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.
|
Antiviral activity against Ebolavirus infected in human HeLa cells after 48 hrs by immuno-staining assay
|
Ebolavirus
|
140.0
nM
|
|
Journal : J Med Chem
Title : The ProTide Prodrug Technology: From the Concept to the Clinic.
Year : 2018
Volume : 61
Issue : 6
First Page : 2211
Last Page : 2226
Authors : Mehellou Y, Rattan HS, Balzarini J.
Abstract : The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.
|
Antiviral activity against Ebolavirus infected in human HuH7 cells after 3 days by end point dilution assay
|
Ebolavirus
|
70.0
nM
|
|
Journal : J Med Chem
Title : The ProTide Prodrug Technology: From the Concept to the Clinic.
Year : 2018
Volume : 61
Issue : 6
First Page : 2211
Last Page : 2226
Authors : Mehellou Y, Rattan HS, Balzarini J.
Abstract : The ProTide technology is a prodrug approach developed for the efficient intracellular delivery of nucleoside analogue monophosphates and monophosphonates. In this approach, the hydroxyls of the monophosphate or monophosphonate groups are masked by an aromatic group and an amino acid ester moiety, which are enzymatically cleaved-off inside cells to release the free nucleoside monophosphate and monophosphonate species. Structurally, this represents the current end-point of an extensive medicinal chemistry endeavor that spans almost three decades. It started from the masking of nucleoside monophosphate and monophosphonate groups by simple alkyl groups and evolved into the sophisticated ProTide system as known today. This technology has been extensively employed in drug discovery, and it has already led to the discovery of two FDA-approved (antiviral) ProTides. In this work, we will review the development of the ProTide technology, its application in drug discovery, and its role in the improvement of drug delivery and efficacy.
|
Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging
|
Homo sapiens
|
760.0
nM
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Determination of antiviral efficacy in high-content imaging assay in Vero E6 cells infected with SARS-CoV-2 (USA-WA1/2020 isolate) at MOI 0.75 after 24 hrs
|
Chlorocebus sabaeus
|
620.0
nM
|
|
Title : A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals
Year : 2020
Authors : Laura Riva, Shuofeng Yuan, Xin Yin, Laura Martin-Sancho, Naoko Matsunaga, Sebastian Burgstaller-Muehlbacher, Lars Pache, Paul P. De Jesus, Mitchell V. Hull, Max Chang, Jasper Fuk-Woo Chan, Jianli Cao, Vincent Kwok-Man Poon, Kristina Herbert, Tu-Trinh Nguyen, Yuan Pu, Courtney Nguyen, Andrey Rubanov, Luis Martinez-Sobrido, Wen-Chun Liu, Lisa Miorin, Kris M. White, Jeffrey R. Johnson, Christopher Benner, Ren Sun, Peter G. Schultz, Andrew Su, Adolfo Garcia-Sastre, Arnab K. Chatterjee, Kwok-Yung Yuen, Sumit K. Chanda
Abstract : The emergence of novel SARS coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of severe pneumonia-like disease designated as coronavirus disease 2019 (COVID-19). To date, more than 2.1 million confirmed cases and 139,500 deaths have been reported worldwide, and there are currently no medical countermeasures available to prevent or treat the disease. As the development of a vaccine could require at least 12-18 months, and the typical timeline from hit finding to drug registration of an antiviral is >10 years, repositioning of known drugs can significantly accelerate the development and deployment of therapies for COVID-19. To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.
|
Antiviral activity against SARS coronavirus infected in primary HAE cells
|
SARS coronavirus
|
69.0
nM
|
|
Journal : ACS Med Chem Lett
Title : Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment.
Year : 2020
Volume : 11
Issue : 7
First Page : 1361
Last Page : 1366
Authors : Yan VC, Muller FL.
Abstract : While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and <i>in vivo</i> efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.
|
Antiviral activity against Middle East respiratory syndrome coronavirus infected in primary HAE cells
|
Middle East respiratory syndrome coronavirus
|
74.0
nM
|
|
Journal : ACS Med Chem Lett
Title : Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment.
Year : 2020
Volume : 11
Issue : 7
First Page : 1361
Last Page : 1366
Authors : Yan VC, Muller FL.
Abstract : While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and <i>in vivo</i> efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.
|
Antiviral activity against 2019-nCoV BetaCoV/Wuhan/WIV04/2019 infected in African green monkey VeroE6 cells assessed as reduction in viral yield preincubated with virus for 1 hr followed by cell infection and measured after 2 hrs by qRT-PCR method
|
Severe acute respiratory syndrome coronavirus 2
|
770.0
nM
|
|
Journal : J Med Chem
Title : Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13205
Last Page : 13227
Authors : Choudhry N,Zhao X,Xu D,Zanin M,Chen W,Yang Z,Chen J
Abstract : The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.
|
Antiviral activity against wild type HCoV-OC43 infected in human Huh-7 cells preincubated for 1 hrs followed by overlaying with reduced-serum Medium and measured after 72 hrs ELISpot assay
|
Human coronavirus OC43
|
150.0
nM
|
|
Journal : J Med Chem
Title : Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13205
Last Page : 13227
Authors : Choudhry N,Zhao X,Xu D,Zanin M,Chen W,Yang Z,Chen J
Abstract : The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.
|
Antiviral activity against HCoV-229E infected in human Huh7 cells assessed as reduction in virus induced cytopathic effect incubated for 6 days by cellTiter-Glo assay
|
Human coronavirus 229E
|
24.0
nM
|
|
Journal : J Med Chem
Title : Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13205
Last Page : 13227
Authors : Choudhry N,Zhao X,Xu D,Zanin M,Chen W,Yang Z,Chen J
Abstract : The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.
|
Antiviral activity against SARS-CoV expressing green fluorescent protein infected in human airway epithelial cells incubated for 48 hrs by RT-PCR method
|
Severe acute respiratory syndrome-related coronavirus
|
60.0
nM
|
|
Journal : J Med Chem
Title : Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Year : 2020
Volume : 63
Issue : 22.0
First Page : 13205
Last Page : 13227
Authors : Choudhry N,Zhao X,Xu D,Zanin M,Chen W,Yang Z,Chen J
Abstract : The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.
|
Antiviral activity against RSV A2 infected in HEp-2 cells assessed as reduction in virus-induced cytopathic effect after 4 days by CellTiter Glo viability assay
|
Human respiratory syncytial virus
|
15.0
nM
|
|
|
Antiviral activity against RSV infected in NHBE cells after 3 days by ONE-Glo luciferase assay
|
Respiratory syncytial virus
|
49.0
nM
|
|
|
Drug metabolism in human HEp-2 cells assessed as 1-NTP metabolite concentration at EC50 over 48 hrs by LC-MS/MS analysis
|
Homo sapiens
|
110.0
nM
|
|
|
Drug metabolism in NHBE cells assessed as 1-NTP metabolite concentration at EC50 over 48 hrs by LC-MS/MS analysis
|
Homo sapiens
|
140.0
nM
|
|
|
Antiviral activity against SARS-CoV-2 infected in 16HBE14o- cells assessed as inhibition of viral replication after 1 day by Nano-Glo luciferase assay
|
Severe acute respiratory syndrome coronavirus 2
|
590.0
nM
|
|
|
Antiviral activity against SARS-CoV-2 infected in Vero E6 cells assessed as inhibition of viral replication measured after 48 hrs by qRT-PCR method
|
Severe acute respiratory syndrome coronavirus 2
|
770.0
nM
|
|
|
Antiviral activity against SARS-CoV-2 nCoV-2019BetaCoV/Wuhan/WIV04/ infected in African green monkey Vero E6 cells assessed as inhibition of viral replication at 5 uM when host cells were pretreated for 1 hr followed by viral infection then followed by removal of infected supernatant and subsequent culture addition with fresh compounds and measured after 24 hrs by qRT-PCR method relative to control
|
Severe acute respiratory syndrome coronavirus 2
|
65.0
%
|
|
|
Antiviral activity against HCoV-OC43 infected in HCT-8 cells assessed as reduction in viral replication treated 1 hr post infection and measured after 120 hrs post infection by MTS cell proliferation colorimetric assay
|
Human coronavirus OC43
|
700.0
nM
|
|
|
Antiviral activity against SARS-COV 2 infected in human Huh-7 cells assessed as inhibition of viral replication at MOI of 0.01 and incubated after 2 hrs post infection for 48 hrs by direct yield reduction assay
|
Severe acute respiratory syndrome coronavirus 2
|
4.0
nM
|
|
|
Antiviral activity against SARS-COV 2 infected in human Caco-2 cells assessed as inhibition of viral replication at MOI of 0.01 and incubated after 2 hrs post infection for 48 hrs by immunodetection assay
|
Severe acute respiratory syndrome coronavirus 2
|
10.0
nM
|
|
|
Antiviral activity against SARS-COV 2 infected in human Calu-3 cells assessed as inhibition of viral replication at MOI of 0.01 and incubated after 2 hrs post infection for 48 hrs by direct yield reduction assay
|
Severe acute respiratory syndrome coronavirus 2
|
110.0
nM
|
|
|
Antiviral activity against SARS-COV 2 infected in human Huh-7 cells
|
Severe acute respiratory syndrome coronavirus 2
|
2.0
nM
|
|
|
Antiviral activity against SARS-COV 2 infected in human Caco-2 cells
|
Severe acute respiratory syndrome coronavirus 2
|
380.0
nM
|
|
|
Antiviral activity against SARS-CoV-2 C-Tan-nCoV Wuhan strain 01 infected in African green monkey Vero cells assessed as inhibition of viral replication measured after 48 hrs by RT-qPCR method
|
Severe acute respiratory syndrome coronavirus 2
|
800.0
nM
|
|
|
Antiviral activity against SARS Cov-2 USA/WA1/2020 infected in Vero E6 cells assessed as reduction in virus-induced cytopathic effect preincubated for 1 hr followed by viral infection and measured after 48 hrs post infection
|
Severe acute respiratory syndrome coronavirus 2
|
850.0
nM
|
|
|
Antiviral activity against SARS coronavirus 2 USA/WA1/2020 infected in Calu-3 cells assessed as reduction in virus-induced cytopathic effect preincubated for 1 hr followed by viral infection and measured after 48 hrs
|
Severe acute respiratory syndrome coronavirus 2
|
60.0
nM
|
|
|
Antiviral activity against Ebola virus trVLP infected in human Huh-7 cells pretreated for 1 hrs followed by viral infection and measured after 24 hrs by dual luciferase reporter assay
|
Ebolavirus
|
320.0
nM
|
|
|
Antiviral activity against SARS-CoV-2 nCoV-2019 BetaCoV/Wuhan/WIV04/2019 infected in African green monkey VeroE6 cells incubated for 48 hrs by qRT-PCR method
|
Severe acute respiratory syndrome coronavirus 2
|
770.0
nM
|
|
|
Antiviral activity against SARS Cov-2 USA_WA1/2020 infected in human Calu-3 cells measured upto 72 hrs by qRT-PCR method
|
Severe acute respiratory syndrome coronavirus 2
|
280.0
nM
|
|
|
Antiviral activity against SARS Cov-2 USA_WA1/2020 infected in HAE cells measured upto 72 hrs by qRT-PCR method
|
Severe acute respiratory syndrome coronavirus 2
|
10.0
nM
|
|
|
Antiviral activity against SARS-CoV-2/NL/2020 infected in African green monkey Vero E6 cells assessed as inhibition of plaque formation measured after 3 days by Plaque reduction assay
|
Severe acute respiratory syndrome coronavirus 2
|
150.0
nM
|
|
|
Antiviral activity against SARS-COV2/Padova/2020 infected in African green monkey Vero E6 cells assessed as inhibition of plaque formation measured after 3 days by Plaque reduction assay
|
Severe acute respiratory syndrome coronavirus 2
|
250.0
nM
|
|
|
Antiviral activity against Severe acute respiratory syndrome coronavirus 2 UC-1074 infected in African green monkey Vero cells assessed as reduction in plaque formation measured after 5 days by microscopic analysis
|
Severe acute respiratory syndrome coronavirus 2
|
870.0
nM
|
|
|
Antiviral activity against Severe acute respiratory syndrome coronavirus 2 UC-1075 infected in African green monkey Vero cells assessed as reduction in plaque formation measured after 5 days by microscopic analysis
|
Severe acute respiratory syndrome coronavirus 2
|
610.0
nM
|
|
