ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by 2019 novel coronavirus (2019-nCoV) has been a crisis of global health, whereas the effective vaccines against 2019-nCoV are still under development. Alternatively, utilization of old drugs or available medicine that can suppress the viral activity or replication may provide an urgent solution to suppress the rapid spread of 2019-nCoV. Andrographolide is a highly abundant natural product of the medicinal plant, Andrographis paniculata, which has been clinically used for inflammatory diseases and anti-viral therapy. We herein demonstrate that both andrographolide and its fluorescent derivative, the nitrobenzoxadiazole-conjugated andrographolide (Andro- NBD), suppressed the main protease (Mpro) activities of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV). Moreover, Andro-NBD was shown to covalently link its fluorescence to these proteases. Further mass spectrometry (MS) analysis suggests that andrographolide formed a covalent bond with the active site Cys145 of either 2019-nCoV Mpro or SARS-CoV Mpro. Consistently, molecular modeling analysis supported the docking of andrographolide within the catalytic pockets of both viral Mpros. Considering that andrographolide is used in clinical practice with acceptable safety and its diverse pharmacological activities that could be beneficial for attenuating COVID-19 symptoms, extensive investigation of andrographolide on the suppression of 2019-nCoV as well as its application in COVID-19 therapy is suggested.
Subject(s)
Cysteine Endopeptidases/metabolism , Diterpenes/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism , Betacoronavirus/enzymology , Catalytic Domain , Coronavirus 3C Proteases , Cysteine Endopeptidases/chemistry , Diterpenes/chemistry , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Molecular Docking Simulation , Protein Conformation , Protein Multimerization , Severe acute respiratory syndrome-related coronavirus/enzymology , SARS-CoV-2 , Viral Nonstructural Proteins/chemistryABSTRACT
BACKGROUND: China was the first country in the world to experience a large-scale COVID-19 outbreak. The rapid spread of the disease and enforcement of public health measures has caused distress among vulnerable populations such as pregnant women. With a limited understanding of the novel, emerging infectious disease, pregnant women have sought ways to access timely and trusted health care information. The mental health status of pregnant women during this public health emergency, as well as how they responded to the situation and where and how they obtained antenatal care information, remain to be understood. OBJECTIVE: This study aimed to evaluate the mental health status of pregnant women during the COVID-19 epidemic in China by measuring their perceived stress, anxiety, and depression levels; explore the approaches used by them to access antenatal health care information; and determine their associations with maternal mental health status. METHODS: We conducted a web-based, cross-sectional survey to assess the mental health status of Chinese pregnant women by using the validated, Chinese version of Perceived Stress Scale, Self-Rating Anxiety Scale, and Edinburgh Depression Scale. We also collected information on the various approaches these women used to access antenatal care information during the early stage of the COVID-19 epidemic, from February 5 to 28, 2020. RESULTS: A total of 1873 pregnant women from 22 provinces or regions of China participated in the survey. The prevalence of perceived stress, anxiety, and depression among these participants was 89.1% (1668/1873; 95% CI 87.6%, 90.4%), 18.1% (339/1873; 95% CI 16.4%, 19.9%), and 45.9% (859/1873; 95% CI 43.6%, 48.1%), respectively. Hospitals' official accounts on the Chinese social media platforms WeChat and Weibo were the most popular channels among these pregnant women to obtain antenatal care information during the COVID-19 outbreak. Access to antenatal care information via the hospitals' official social media accounts was found to be associated with a significantly lower risk of perceived stress (adjusted odds ratio [aOR] 0.46, 95% CI 0.30-0.72; P=.001), anxiety (aOR 0.53, 95% CI 0.41-0.68; P<.001), and depression (aOR 0.73, 95% CI 0.59-0.91; P=.005). Access to health care information via hospital hotlines or SMS was found to be significantly associated with a lower risk of anxiety only (OR 0.77, 95% CI 0.60-0.98; P=.04). CONCLUSIONS: During the COVID-19 outbreak in China, pregnant women experienced high levels of perceived stress, anxiety, and depression. During such public health emergencies, mental health care services should be strengthened to reassure and support pregnant women. Specific information targeted at pregnant women, including information on how to cope in an emergency or major disease outbreak, developed and disseminated by health care institutions via social media platforms could be an effective way to mitigate mental health challenges and ensure epidemic preparedness and response in the future.