Pathomechanisms, therapeutic targets and potent inhibitors of some beta-coronaviruses from bench-to-bedside.

Since the emergence of their primitive strains, the complexity surrounding their pathogenesis, constant genetic mutation and translation are contributing factors to the scarcity of a successful vaccine for coronaviruses till moment. Although, the recent announcement of vaccine breakthrough for COVID-19 renews the hope, however, there remains a major challenge of accessibility to urgently match the rapid global therapeutic demand for curtailing the pandemic, thereby creating an impetus for further search. The reassessment of results from a stream of experiments is of enormous importance in identifying bona fide lead-like candidates to fulfil this quest. This review comprehensively highlights the common pathomechanisms and pharmacological targets of HCoV-OC43, SARS-CoV-1, MERS-CoV and SARS-CoV-2, and potent therapeutic potentials from basic and clinical experimental investigations. The implicated targets for the prevention and treatment include the viral proteases (Mpro, PLpro, 3CLpro), viral structural proteins (S- and N-proteins), non-structural proteins (nsp 3, 8, 10, 14, 16), accessory protein (ns12.9), viroporins (3a, E, 8a), enzymes (RdRp, TMPRSS2, ADP-ribosyltransferase, MTase, 2'-O-MTase, TATase, furin, cathepsin, deamidated human triosephosphate isomerase), kinases (MAPK, ERK, PI3K, mTOR, AKT, Abl2), interleukin-6 receptor (IL-6R) and the human host receptor, ACE2. Notably among the 109 overviewed inhibitors include quercetin, eriodictyol, baicalin, luteolin, melatonin, resveratrol and berberine from natural products, GC373, NP164 and HR2P-M2 from peptides, 5F9, m336 and MERS-GD27 from specific human antibodies, imatinib, remdesivir, ivermectin, chloroquine, hydroxychloroquine, nafamostat, interferon-ß and HCQ from repurposing libraries, some iron chelators and traditional medicines. This review represents a model for further translational studies for effective anti-CoV therapeutic designs.

The first cohort of the COVID-19 patients in Vietnam and the national response to the pandemic.

The COVID-19 pandemic is a novel infectious disease pandemic with the agent SARS-CoV-2 virus which is currently affecting and causing damage globally. The outbreak has been crossing over 200 countries in the world. In the situation of the outbreak of COVID-19, Vietnam has first sixteen typical cases confirmed positive updated to Feb 28th, 2020. After completely applying the medical prevention and active control, Vietnam has the ability to take control of the outbreak of COVID-19 as a recent of WHO assessment. Vietnam has been reported as an effective country for prevention and control the outbreak of COVID-19. We retroactive reviewed our experience with 16 positive cases isolation. This article aims to present the first cohort of COVID-19 patients updated to Feb 28th, 2020 in Vietnam and sharing the national response to the pandemic.

A cross-sectional study of immune seroconversion to SARS-CoV-2 in frontline maternity health professionals.

COVID-19, the respiratory disease caused by SARS-CoV-2, is thought to cause a milder illness in pregnancy with a greater proportion of asymptomatic carriers. This has important implications for the risk of patient-to-staff, staff-to-staff and staff-to-patient transmission among health professionals in maternity units. The aim of this study was to investigate the prevalence of previously undiagnosed SARS-CoV-2 infection in health professionals from two tertiary-level maternity units in London, UK, and to determine associations between healthcare workers' characteristics, reported symptoms and serological evidence of prior SARS-CoV-2 infection. In total, 200 anaesthetists, midwives and obstetricians, with no previously confirmed diagnosis of COVID-19, were tested for immune seroconversion using laboratory IgG assays. Comprehensive symptom and medical histories were also collected. Five out of 40 (12.5%; 95%CI 4.2-26.8%) anaesthetists, 7/52 (13.5%; 95%CI 5.6-25.8%) obstetricians and 17/108 (15.7%; 95%CI 9.5-24.0%) midwives were seropositive, with an overall total of 29/200 (14.5%; 95%CI 9.9-20.1%) of maternity healthcare workers testing positive for IgG antibodies against SARS-CoV-2. Of those who had seroconverted, 10/29 (35.5%) were completely asymptomatic. Fever or cough were only present in 6/29 (21%) and 10/29 (35%) respectively. Anosmia was the most common symptom occurring in 15/29 (52%) seropositive participants and was the only symptom that was predictive of positive seroconversion (OR 18; 95%CI 6-55). Of those who were seropositive, 59% had not self-isolated at any point and continued to provide patient care in the hospital setting. This is the largest study of baseline immune seroconversion in maternity healthcare workers conducted to date and reveals that one out of six were seropositive, of whom one out of three were asymptomatic. This has significant implications for the risk of occupational transmission of SARS-CoV-2 for both staff and patients in maternity units. Regular testing of staff, including asymptomatic staff should be considered to reduce transmission risk.

Immuno-pathogenesis of nCOVID-19 and a possible host-directed therapy including anti-inflammatory and anti-viral prostaglandin (PG J2) for effective treatment and reduction in the death toll.

Coronaviruses including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also known as 2019-nCoV especially in China) replicate and divide in host cells. During this they are partly hidden from the innate immune responses although inflammatory consequences of viral replication still occur. We propose that anti-inflammatory antiviral prostaglandins may not only restrict viral replication but also prevent inflammatory responses in the lungs and other vital organs that are known to be part of the immuno-pathogenesis of coronavirus disease-19 (COVID-19). The combination of anti-inflammatory antiviral prostaglandins with interferons may lead to the clearance of viruses inside growth-restricted infected cells. However, further experimental studies and clinical trials should be conducted to evaluate the safety and efficacy of these possible therapies.

Diagnosis and treatment of novel coronavirus pneumonia based on the theory of traditional Chinese medicine.

Since the outbreak of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19), it has rapidly spread to 187 countries, causing serious harm to the health of people and a huge social burden. However, currently, drugs specifically approved for clinical use are not available, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.

2019_nCoV/SARS-CoV-2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses.

The current outbreak of a novel severe acute respiratory syndrome-like coronavirus, 2019_nCoV (now named SARS-CoV-2), illustrated difficulties in identifying a novel coronavirus and its natural host, as the coding sequences of various Betacoronavirus species can be highly diverse. By means of whole-genome sequence comparisons, we demonstrate that the noncoding flanks of the viral genome can be used to correctly separate the recognized four betacoronavirus subspecies. The conservation would be sufficient to define target sequences that could, in theory, classify novel virus species into their subspecies. Only 253 upstream noncoding sequences of Sarbecovirus are sufficient to identify genetic similarities between species of this subgenus. Furthermore, it was investigated which bat species have commercial value in China, and would thus likely be handled for trading purposes. A number of coronavirus genomes have been published that were obtained from such bat species. These bats are used in Traditional Chinese Medicine, and their handling poses a potential risk to cause zoonotic coronavirus epidemics. SIGNIFICANCE AND IMPACT OF THE STUDY: The noncoding upstream and downstream flanks of coronavirus genomes allow for rapid classification of novel Betacoronavirus species and correct identification of genetic relationships. Although bats are the likely natural host of 2019_nCoV, the exact bat species that serves as the natural host of the virus remains as yet unknown. Chinese bat species with commercial value were identified as natural reservoirs of coronaviruses and are used in Traditional Chinese Medicine. Since their trading provides a potential risk for spreading zoonoses, a change in these practices is highly recommended.

[Avian infectious bronchitis disease in Tunisia: seroprevalence, pathogenicity and compatibility studies of vaccine-field isolates]. / La bronchite infectieuse aviaire en Tunisie: séroprévalence, pathogénicité et étude de compatibilité vaccin-isolats.

A sero-epidemiological study was carried out on 5660 sera collected, between 2006 and 2008, from different flocks in different regions of the country. The ELISA results showed low levels of antibodies indicating vaccination failures. 45 to 69% of the flocks showed positive levels of antibodies and only 5 to 15% of these were protected. The pathogenicity studies of the Tunisian field isolates TN20/00 and TN335/01 demonstrated high clinical and lesion scores indicating the pathogenic effect of the two isolates. The challenge experiments conducted to evaluate the cross-protection between the H120 vaccine and the field isolates showed low protection rate, especially against the TN20/00 virus. The overall results allowed the determination of the pathogenic nature of the field isolates and a vaccination program based on the use of the only Massachusetts H120 strain did not reduce tracheal and kidney lesions. To better control the disease, adapting the vaccination program by using vaccine allowing better protection against variant strains, is recommended.