Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused devastating impacts on the public health and the global economy. Rapid viral antigenic evolution has led to the continual generation of new variants. Of special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies (nAbs). This has posed new challenges for the prevention and treatment of COVID-19. Therefore, exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain (RBD), the S2 fusion subunit has remained highly conserved among variants. Hence, S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 variants. Here, we summarize the most recently developed broad-spectrum fusion inhibitors (e.g., nAbs, peptides, proteins, and small-molecule compounds) and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 subunit. The main focus includes all the targetable S2 elements, namely, the fusion peptide, stem helix, and heptad repeats 1 and 2 (HR1-HR2) bundle. Moreover, we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors, which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses. 

/pdf/targetable-elements-in-sars-cov-2-s2-subunit-for-the-design-1tffpnc6.pdf

Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines

The COVID-19 pandemic, caused by SARS-CoV-2, has had a huge impact on global health. To respond to rapidly mutating viruses and to prepare for the next pandemic, there is an urgent need to develop small molecule therapies that target critical stages of the SARS-CoV-2 life cycle. Inhibiting the entry process of the virus can effectively control viral infection and play a role in prevention and treatment. Host factors involved in this process, such as ACE2, TMPRSS2, ADAM17, furin, PIKfyve, TPC2, CTSL, AAK1, V-ATPase, HSPG, and NRP1, have been found to be potentially good targets with stability. Through further exploration of the cell entry process of SARS-CoV-2, small-molecule drugs targeting these host factors have been developed. This review focuses on the structural functions of potential host cell targets during the entry of SARS-CoV-2 into host cells. The research progress, chemical structure, structure-activity relationship, and clinical value of small-molecule inhibitors against COVID-19 are reviewed to provide a reference for the development of small-molecule drugs against COVID-19. 

Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors.

Since the SARS-CoV-2 outbreak, pharmaceutical companies and researchers worldwide have worked hard to develop vaccines and drugs to end the SARS-CoV-2 pandemic. The potential pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, belongs to a novel lineage of beta coronaviruses in the subgenus arbovirus. Antiviral drugs, convalescent plasma, monoclonal antibodies, and vaccines are effective treatments for SARS-CoV-2 and are beneficial in preventing infection. Numerous studies have already been conducted using the genome sequence of SARS-CoV-2 in comparison with that of other SARS-like viruses, and numerous treatments/prevention measures are currently undergoing or have already undergone clinical trials. We summarize these studies in depth in the hopes of highlighting some key details that will help us to better understand the viral origin, epidemiology, and treatments of the virus.

/pdf/sars-cov-2-an-updated-review-highlighting-its-evolution-and-uoqrlcol.pdf

SARS-CoV-2: An Updated Review Highlighting Its Evolution and Treatments

To understand Baduanjin rehabilitation therapy in mild COVID‐19 patients.

What can we learn from the Baduanjin rehabilitation as COVID‐19 treatment?: A narrative review

This article reviews various aspects of COVID-19, including its current status, its side-effects, emergency protective measures and strategies from lifestyle to traditional Chinese medicine (TCM) for fighting against the SARS-CoV-2, and its major variants (Delta and Omicron), with the ongoing global COVID-19 pandemic, which include "Carassius auratus lifestyle" for high effective isolation, social and high-tech medical strategies, traditional Chinese herbs "Bark-Flower-Fruit-Grass-Leaf-Nucleolus(seed)-Root (BFFGLNR)", and the combination of Chinese and western medicine. As a choice, little is known whether the Chinese acupuncture is an effective method for confirming and suspecting COVID-19 patients, which include imported and asymptomatic cases. Definitely, acupuncture has been proven effective treatment for the recovery of COVID-19 cases. However, further animal experiments and clinical trials are required to confirm its effects and disclose underlying mechanisms. In conclusion, these emergency protective measures and strategies for COVID-19 will help to effectively combat the SARS-CoV-2 and its variants during the pandemic and post-COVID-19 era. 

https://doi.org/10.1016/j.ccmp.2023.100089

Emergency Protective Measures and Strategies of COVID-19: From Lifestyle to Traditional Chinese Medicine

OBJECTIVE: To compare the clinical therapeutic effect on coronavirus disease 2019 (COVID-19) with insomnia between the combined treatment of baduanjin and auricular point sticking therapy and the medication with oral estazolam on the base of the conventional treatment METHODS: A total of 90 patients with COVID-19 accompanied with insomnia were randomly divided into an observation group (45 cases, 3 cases dropped off) and a control group (45 cases) In the observation group, baduanjin, a traditional Chinese fitness activity, was practiced everyday Besides, auricular point sticking therapy was exerted at ear-shenmen (TF 4), subcortex (AT 4), heart (CO 15), occiput (AT 3), etc These auricular points were pressed and kneaded three times a day, 30 s at each point each time, consecutively for 12 days In the control group, estazolam tablets were prescribed for oral administration, 1 mg, once daily, consecutively for 12 days Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS) and the score of symptoms in traditional Chinese medicine (TCM) were observed in the two groups and the clinical therapeutic effect was evaluated RESULTS: After treatment, the scores of every item and the total scores in PSQI were all reduced as compared with those before treatment in the two groups (P 005) CONCLUSION: The combined treatment of baduanjin and auricular point sticking therapy improves sleep quality, the conditions of anxiety and depression and the symptoms in TCM for patients of COVID-19 with insomnia The therapeutic effect of this combined treatment is better than the oral administration of estazolam

Observation of therapeutic effect on coronavirus disease 2019 with insomnia in treatment with baduanjin and auricular point sticking therapy

Abstract Background: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. Methods: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. Results: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. Trial registration: Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1

https://doi.org/10.1097/cm9.0000000000002104

A trial of arbidol hydrochloride in adults with COVID-19

Aim The present study aimed to evaluate the durability of immune response after basic and booster immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver disease (CLD). Methods Patients with CLD and complete basic or booster immunization with SARS-CoV-2 vaccines were included in this study. Based on the vaccination situation, they were divided into the basic immunity group (Basic) and the booster immunity group (Booster), which were then subdivided into four groups according to the time interval from completion of basic immunization or booster immunization to serological specimen collection. The positive rates and antibody titers of novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD) were analyzed. Results A total of 313 patients with CLD were enrolled in this study, including 201 in Basic and 112 in Booster. The positive rates of nCoV NTAb and nCoV S-RBD within 30 days of completing basic immunization were 80.4% and 84.8%, respectively, but decreased rapidly with the extension of vaccination time, and only 29% and 48.4% of patients with CLD remained positive for nCoV NTAb and nCoV S-RBD, respectively, after 120 days of completing basic immunization. Within 30 days of booster immunization, the positive rates of nCoV NTAb and nCoV S-RBD in patients with CLD rapidly increased from 29.0% and 48.4% at the end of basic immunization to 95.2% and 90.5%, and maintained a high level (defined as the positive rate >50%) until 120 days when the positive rates of nCoV NTAb and nCoV S-RBD were still high at 79.5% and 87.2%, respectively. After basic immunization, the time for nCoV NTAb and nCoV S-RBD to turn negative was 120 and 169 days, respectively, and the negative time of nCoV NTAb and nCoV S-RBD was significantly prolonged to 266 days and 329 days, respectively. Conclusion It is safe and effective for patients with CLD to complete basic and booster immunization with SARS-CoV-2 vaccines. After booster immunization, the immune response of patients with CLD was further improved and the durability of the SARS-CoV-2 antibody was significantly prolonged.

/pdf/durability-of-immune-response-after-sars-cov-2-vaccination-23l6ej7g.pdf

Durability of immune response after SARS-CoV-2 vaccination in patients with chronic liver disease

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Observation of therapeutic effect on coronavirus disease 2019 with insomnia in treatment with baduanjin and auricular point sticking therapy

A trial of arbidol hydrochloride in adults with COVID-19

Durability of immune response after SARS-CoV-2 vaccination in patients with chronic liver disease