Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV
Antiviral Res. 2023 Oct 18;219:105733. doi: 10.1016/j.antiviral.2023.105733. Online ahead of print.ABSTRACTHerpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivat...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: David I Bernstein Nancy M Sawtell Fernando J Bravo David A Dixon Christian Gege Gerald Kleymann Source Type: research
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors
Antiviral Res. 2023 Oct 18;219:105735. doi: 10.1016/j.antiviral.2023.105735. Online ahead of print.ABSTRACTA class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 μM by pre-in...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Srinivasa Rao Palla Chen-Wei Li Tai-Ling Chao Hoi-Ling Vienn Lo Jia-Jin Liu Max Yu-Chen Pan Yu-Ting Chiu Wen-Chin Lin Chih-Wei Hu Chuen-Mi Yang Yi-Ying Chen Jun-Tung Fang Sheng-Wei Lin Yi-Tzu Lin Hsiao-Ching Lin Chih-Jung Kuo Lily Hui-Ching Wang Sui-Yuan Source Type: research
ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2
Antiviral Res. 2023 Oct 18:105736. doi: 10.1016/j.antiviral.2023.105736. Online ahead of print.ABSTRACTApoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus infection activates ASK1 related p...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Wael L Demian Rajesh Abraham Jacob Olga Cormier Aisha Nazli Matthew Melki Akarin Asavajaru Kaushal Baid Ali Zhang Matthew S Miller Charu Kaushic Arinjay Banerjee Karen Mossman Source Type: research
Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV
Antiviral Res. 2023 Oct 18;219:105733. doi: 10.1016/j.antiviral.2023.105733. Online ahead of print.ABSTRACTHerpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivat...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: David I Bernstein Nancy M Sawtell Fernando J Bravo David A Dixon Christian Gege Gerald Kleymann Source Type: research
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors
Antiviral Res. 2023 Oct 17:105735. doi: 10.1016/j.antiviral.2023.105735. Online ahead of print.ABSTRACTA class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 μM by pre-incuba...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Srinivasa Rao Palla Chen-Wei Li Tai-Ling Chao Hoi-Ling Vienn Lo Liu Jia-Jin Max Yu-Chen Pan Yu-Ting Chiu Wen-Chin Lin Chih-Wei Hu Chuen-Mi Yang Yi-Ying Chen Jun-Tung Fang Sheng-Wei Lin Yi-Tzu Lin Hsiao-Ching Lin Chih-Jung Kuo Lily Hui-Ching Wang Sui-Yuan Source Type: research
ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2
Antiviral Res. 2023 Oct 18:105736. doi: 10.1016/j.antiviral.2023.105736. Online ahead of print.ABSTRACTApoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus infection activates ASK1 related p...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Wael L Demian Rajesh Abraham Jacob Olga Cormier Aisha Nazli Matthew Melki Akarin Asavajaru Kaushal Baid Ali Zhang Matthew S Miller Charu Kaushic Arinjay Banerjee Karen Mossman Source Type: research
Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV
Antiviral Res. 2023 Oct 18;219:105733. doi: 10.1016/j.antiviral.2023.105733. Online ahead of print.ABSTRACTHerpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivat...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: David I Bernstein Nancy M Sawtell Fernando J Bravo David A Dixon Christian Gege Gerald Kleymann Source Type: research
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors
Antiviral Res. 2023 Oct 17:105735. doi: 10.1016/j.antiviral.2023.105735. Online ahead of print.ABSTRACTA class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 μM by pre-incuba...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Srinivasa Rao Palla Chen-Wei Li Tai-Ling Chao Hoi-Ling Vienn Lo Liu Jia-Jin Max Yu-Chen Pan Yu-Ting Chiu Wen-Chin Lin Chih-Wei Hu Chuen-Mi Yang Yi-Ying Chen Jun-Tung Fang Sheng-Wei Lin Yi-Tzu Lin Hsiao-Ching Lin Chih-Jung Kuo Lily Hui-Ching Wang Sui-Yuan Source Type: research
ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2
Antiviral Res. 2023 Oct 18:105736. doi: 10.1016/j.antiviral.2023.105736. Online ahead of print.ABSTRACTApoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus infection activates ASK1 related p...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Wael L Demian Rajesh Abraham Jacob Olga Cormier Aisha Nazli Matthew Melki Akarin Asavajaru Kaushal Baid Ali Zhang Matthew S Miller Charu Kaushic Arinjay Banerjee Karen Mossman Source Type: research
Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV
Antiviral Res. 2023 Oct 17:105733. doi: 10.1016/j.antiviral.2023.105733. Online ahead of print.ABSTRACTHerpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation ...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: David I Bernstein Nancy M Sawtell Fernando J Bravo David A Dixon Christian Gege Gerald Kleymann Source Type: research
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors
Antiviral Res. 2023 Oct 17:105735. doi: 10.1016/j.antiviral.2023.105735. Online ahead of print.ABSTRACTA class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 μM by pre-incuba...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Srinivasa Rao Palla Chen-Wei Li Tai-Ling Chao Hoi-Ling Vienn Lo Liu Jia-Jin Max Yu-Chen Pan Yu-Ting Chiu Wen-Chin Lin Chih-Wei Hu Chuen-Mi Yang Yi-Ying Chen Jun-Tung Fang Sheng-Wei Lin Yi-Tzu Lin Hsiao-Ching Lin Chih-Jung Kuo Lily Hui-Ching Wang Sui-Yuan Source Type: research
ASK1 inhibitors are potential pan-antiviral drugs, which dampen replication of diverse viruses including SARS-CoV2
Antiviral Res. 2023 Oct 18:105736. doi: 10.1016/j.antiviral.2023.105736. Online ahead of print.ABSTRACTApoptosis signal-regulating kinase 1 (ASK1)/MAP3K5 is a stress response kinase that is activated by various stimuli. It is known as an upstream activator of p38- Mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) that are reactive oxygen species (ROS)-induced kinases. Accumulating evidence show that ROS accumulate in virus-infected cells. Here, we investigated the relationship between viruses and ASK1/p38MAPK or ASK1/JNK pathways. Our findings suggest that virus infection activates ASK1 related p...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Wael L Demian Rajesh Abraham Jacob Olga Cormier Aisha Nazli Matthew Melki Akarin Asavajaru Kaushal Baid Ali Zhang Matthew S Miller Charu Kaushic Arinjay Banerjee Karen Mossman Source Type: research
Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV
Antiviral Res. 2023 Oct 17:105733. doi: 10.1016/j.antiviral.2023.105733. Online ahead of print.ABSTRACTHerpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation ...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: David I Bernstein Nancy M Sawtell Fernando J Bravo David A Dixon Christian Gege Gerald Kleymann Source Type: research
Synthesis, evaluation, and mechanism of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones as potent reversible SARS-CoV-2 entry inhibitors
Antiviral Res. 2023 Oct 17:105735. doi: 10.1016/j.antiviral.2023.105735. Online ahead of print.ABSTRACTA class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 μM by pre-incuba...
Source: Antiviral Research - October 20, 2023 Category: Virology Authors: Srinivasa Rao Palla Chen-Wei Li Tai-Ling Chao Hoi-Ling Vienn Lo Liu Jia-Jin Max Yu-Chen Pan Yu-Ting Chiu Wen-Chin Lin Chih-Wei Hu Chuen-Mi Yang Yi-Ying Chen Jun-Tung Fang Sheng-Wei Lin Yi-Tzu Lin Hsiao-Ching Lin Chih-Jung Kuo Lily Hui-Ching Wang Sui-Yuan Source Type: research
Mechanisms of antiviral activity of the new hDHODH inhibitor MEDS433 against respiratory syncytial virus replication
Antiviral Res. 2023 Oct 16:105734. doi: 10.1016/j.antiviral.2023.105734. Online ahead of print.ABSTRACTHuman respiratory syncytial virus (RSV) is an important cause of acute lower respiratory infections, for which no effective drugs are currently available. The development of new effective anti-RSV agents is therefore an urgent priority, and Host-Targeting Antivirals (HTAs) can be considered to target RSV infections. As a contribution to this antiviral avenue, we have characterized the molecular mechanisms of the anti-RSV activity of MEDS433, a new inhibitor of human dihydroorotate dehydrogenase (hDHODH), a key cellular en...
Source: Antiviral Research - October 18, 2023 Category: Virology Authors: Anna Luganini Giulia Sibille Marta Pavan Maurizia Mello Grand Stefano Sainas Donatella Boschi Marco L Lolli Giovanna Chiorino Giorgio Gribaudo Source Type: research
