Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Long-term Therapeutic Observation of Acupuncture at Phenomaxillary Ganglia for Allergic Rhinitis / 上海针灸杂志

ObjectiveTo observe the short-term and long-term efficacies of acupuncture at phenomaxillary ganglia in treating allergic rhinitis.MethodThe recruited subjects were intervened by acupuncture at phenomaxillary ganglia, once a week and 6 times asa treatment course. Visual Analogue Scale (VAS) was adopted to evaluate the general condition and nasal symptoms, and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used to estimate the quality of life (QOL). The evaluations were performed before and after intervention, as well as 2 years after the intervention.ResultThe subjects all had significant improvements in the clinical symptoms after 6 sessions, and the VAS scores of the general conditional nasal symptoms and RQLQ score were significantly decreased (P0.05).ConclusionAcupuncture at phenomaxillary ganglia is effective in treating allergic rhinitis, and the efficacy lasts stably within 2 years.

Cumulative Analgesic Effect of Electroacupuncture at Sanyinjiao (SP6), Xuanzhong (GB39) and Non-acupoint for Primary Dysmenorrhea：A Comparative Study / 上海针灸杂志

Objective To compare the cumulative analgesic effects of electroacupuncture at Sanyinjiao (SP6), Xuanzhong (GB39) and non-acupoint in treating primary dysmenorrhea. Method By adopting a multi-centered randomized controlled study method, 501 patients recruited from Dongzhimen Hospital of Beijing University of Chinese Medicine, China-Japan Friendship Hospital, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Huguosi Hospital of Chinese Medicine of Beijing University of Chinese Medicine and the Outpatient of Shandong University of Traditional Chinese Medicine were randomized into a Sanyinjiao group, a Xuanzhong group, and a non-acupoint group, 167 subjects in each group. The electroacupuncture intervention was applied when dysmenorrhea flared up and the Visual Analogue Scale (VAS) ≥40 mm, with frequency at 2/100 Hz and intensity during patient’s endurance, 30 min each time, once a day, and for successive 3 d. Before the first treatment, 30 min after the first treatment, and respectively prior to the second and third treatment, VAS was used to measure the pain intensity. Meanwhile, the Retrospective Symptom Scale (RSS-COX 2) was investigated before the first treatment, right after the removal of needles for the first treatment, before the second and third treatment. Result The decrease of VAS in Sanyinjiao group was more significant than that in Xuanzhong group and non-acupoint group (MD=﹣2.92 mm, P=0.028; MD=﹣3.47 mm, P=0.009), while there was no significant difference between Xuanzhong group and non-acupoint group (MD=﹣0.56 mm, P=0.674); there were no significant differences in comparing the RSS-COX2 total score among the three groups (P=0.086). Conclusion Sanyinjiao (SP6) can produce a more significant cumulative analgesic effect for primary dysmenorrhea patient than Xuanzhong and non-acupoint, and the effects of Xuanzhong and non-acupoit are equivalent.