Approved COVID-19 vaccines to date have limited effectiveness in protecting infection and blocking transmission. A nasal spray of broad-spectrum antibody against COVID-19 (SA58 Nasal Spray) has recently been developed by Sinovac Life Sciences Co., Ltd.. From October 31 to November 30, 2022, an open-label, blank controlled study on the SA58 Nasal Spray against COVID-19 infection was conducted with the medical personnel working in the designated COVID-19 hospitals and Fangcang shelter hospitals (alternate care sites) of COVID-19 cases in Hohhot city, the Inner Mongolia Autonomous Region. A total of 6662 medical personnel were involved in this study: 3368 used SA58 Nasal Spray from the drug group, and 3294 not used from blank control group. The medication was self-administered intranasally 1~2 times per day with an interval of 6 hours for 30 days.. The safety results indicated that the SA58 Nasal Spray was well tolerant. The incidence of adverse events (AEs) was 28.6% (497/1736), and the majority of the AEs were mild and from administrative site. 135 COVID-19 cases were identified for SARS-CoV-2 by RT-PCR during the 30-day observation. The cumulative incidence of COVID-19 in the drug group and the control group were 0.026% and 0.116%, respectively. The effectiveness of the SA58 Nasal Spray for preventing COVID-19 infection among medical personnel was evaluated as 77.7% (95% CI: 52.2% - 89.6%). In conclusion, the SA58 Nasal Spray is well-tolerant and highly effective against COVID-19 infection.
Background: China witnessed a surge of Omicron infections after abandoning zero COVID strategies on December 7, 2022. The authorities report very sparse deaths based on very restricted criteria, but massive deaths are speculated. Methods: We aimed to estimate the COVID-19 fatalities in Mainland China until summer 2023 using the experiences of Hong Kong and of South Korea in 2022 as prototypes. Both these locations experienced massive Omicron waves after having had very few SARS-CoV-2 infections during 2020-2021. We estimated age-stratified infection fatality rates (IFRs) in Hong Kong and South Korea during 2022 and extrapolated to the population age structure of Mainland China. We also accounted separately for deaths of residents in long-term care facilities, which were prominent in Hong Kong. Results: IFR estimates in non-elderly strata were modestly higher in Hong Kong than South Korea and projected 987,455 and 811,571 maximal COVID-19 deaths, respectively, if the entire China population was infected. Expected COVID-19 deaths in Mainland China until summer 2023 ranged from 64,573 to 691,219 assuming 25-70% of the non-elderly population being infected and variable protection of elderly (from none to three-quarter reduction in fatalities). The main analysis (45% of non-elderly population infected and fatality impact among elderly reduced by half) estimated 199,223-249,094 COVID-19 deaths until summer 2023. Large uncertainties exist regarding potential changes in dominant variant, health system strain, and impact on non-COVID-19 deaths. Conclusions: The most critical factor that can affect total COVID-19 fatalities in China is the extent to which the elderly can be protected.
Background: There is limited information on the role of individuals in different age groups in the spread of infection during the Omicron epidemics, especially ones beyond the winter epidemic wave in 2021-2022. In England, booster vaccination against SARS-CoV-2 is currently restricted to persons aged over 50y and individuals in clinical risk groups. Methods: We used a previously developed methodology to evaluate the role of individuals in different age groups in propagating the Spring, Summer, and Autumn waves of the Omicron epidemic in England. This methodology utilizes the relative risk (RR) statistic that measures the change in the proportion of cases in each age group among all COVID-19 cases in the population before the peak of an epidemic wave vs. after the peak of an epidemic wave. Higher values for the RR statistic represent age groups that experienced a disproportionate depletion of susceptible individuals during the ascent of the epidemic (due to increased contact rates and/or susceptibility to infection). Results: For the 2022 Spring wave, the highest RR estimate belonged to children aged 5 to 9y (RR=2.05 (95%CI (2.02,2.08)), followed by children aged 10 to 14y (RR=1.68 (1.66,1.7)) and children aged 0 to 4y (RR=1.38 (1.36,1.41)). For the Summer wave, the highest RR estimates belonged to persons aged 20 to 34y: (RR=1.09 (1.07,1.12) in aged 20 to 24y, RR=1.09 (1.07,1.11) in aged 25 to 29y, RR=1.09(1.07,1.11) in aged 30 to 34y). For the Autumn wave, the highest RR estimate in adults belonged to those aged 70 to 74y (RR=1.10 (1.07,1.14)), followed by adults aged 35 to 39y (RR=1.09 (1.06,1.12)), adults aged 40 to 44y (RR=1.09 (1.06,1.12)), and adults aged 65 to 69y (RR=1.08 (1.05,1.11)) (with children excluded from the analyses due to limited/irregular detection of COVID-19 cases in children during the Autumn wave). Conclusions: As time progressed, ages of individuals who played the leading roles in propagating the Omicron epidemic waves in England shifted upward, with the leading roles in propagating COVID-19 epidemics in England currently belonging to adults of different ages. Extending booster vaccination to adults aged under 50y, and possibly to children should help limit the spread of Omicron infections in the community.
Background: Data on effectiveness of sotrovimab preventing COVID-19-related hospitalization or mortality, particularly after the emergence of the Omicron variant, are limited. Method: Determine the real-world clinical effectiveness of sotrovimab for prevention of 30-day COVID-19 related hospitalization or mortality using a retrospective cohort within the U.S. Department of Veterans Affairs (VA) healthcare system. Veterans aged ≥18 years, diagnosed with COVID-19 between December 1, 2021, and April 4, 2022, were included. Sotrovimab recipients (n=2,816) were exactly matched to untreated controls (n=11,250) on date of diagnosis, vaccination status, and region. The primary outcome was COVID-19-related hospitalization or all-cause mortality within 30 days from diagnosis. Cox proportional hazards modeling estimated the hazard ratios (HR) and 95% Confidence Interval (CI) for the association between receipt of sotrovimab and outcomes. Results: During BA.1 dominance, compared to matched controls, sotrovimab-treated patients had a 70% lower risk hospitalization within 30 days or mortality (HR 0.30; 95%CI, 0.23-0.40), a 66% lower risk of 30-day hospitalization (HR 0.34; 95%CI, 0.25-0.46), and a 77% lower risk of 30-day all-cause mortality (HR 0.23; 95%CI, 0.14-0.38). During BA.2 dominance sotrovimab-treated patients had a 71% (HR .29; 95%CI, 0.08-0.98) lower risk of 30-day COVID-19-related- hospitalization, emergency, or urgent care. Limitations include confounding by indication. Conclusions: Using national real-world data from high risk and predominantly vaccinated Veterans, administration of sotrovimab, compared with no treatment, was associated with reduced risk of 30-day COVID-19-related hospitalization or all-cause mortality during the Omicron BA.1 period and reduced risk of progression to severe COVID-19 during the BA.2 dominant period.
In this paper, our objective was to investigate whether the Covid-19 pandemic disease is more likely to break out in some specific age group or not. We also intended to know whether some specific demographic parameters like birth rate, death rate controls the spreading of the disease. Our investigation showed that the post reproductive population group is more prone to the disease for the countries having population pyramid of stationary or con-tracting type where as for the countries with expanding population pyramid, the pre reproductive population is more likely to be attacked by the disease. We also found the domains of values of the demographic parameters that result different dynamic phenomena. Further we tried to know whether a countrys9 population pyramid has an effect in spreading the disease. Our experiment showed that for countries having expanding population pyramid, the total number of cases is expected to be comparatively low whereas for countries having contracting population pyramid, the total number of cases is expected to be comparatively high.
Throughout the SARS-CoV-2 pandemic, Germany lacked an adaptive population panel for epidemic diseases and a modelling platform to rapidly incorporate panel estimates. We evaluated how a cross-sectional analysis of 9922 participants of the MuSPAD study in June/July 2022 combined with a newly developed modelling platform could bridge the gap and analyzed antibody levels, neutralizing serum activity and interferon-gamma release response of serum samples. We categorized the population into four groups with differing protection against severe course of disease (validated by neutralizing serum activity), and found that 30% were in the group with highest protection, and 85% in either the highest categories or second highest group regarding protection level. Estimated hospitalizations due to SARS-CoV-2 were predicted to be between 30 to 300% of the peak in 02/2021 dependent on assumed variant characteristics. We showed the feasibility of a rapid epidemic panel able to evaluate complex endpoints for SARS-CoV-2 and inform scenario modelling.
Background: The COVID-19 pandemic has claimed numerous lives in the last three years. With new variants emerging every now and then, the world is still battling with the management of COVID-19. Purpose: To utilize a deep learning model for the automatic detection of severity scores from chest CT scans of COVID-19 patients and compare its diagnostic performance with experienced human readers. Methods: A deep learning model capable of identifying consolidations and ground-glass opacities from the chest CT images of COVID-19 patients was used to provide CT severity scores on a 25-point scale for definitive pathogen diagnosis. The model was tested on a dataset of 469 confirmed COVID-19 cases from a tertiary care hospital. The quantitative diagnostic performance of the model was compared with three experienced human readers. Results: The test dataset consisted of 469 CT scans from 292 male (average age: 52.30) and 177 female (average age: 53.47) patients. The standalone model had an MAE of 3.192, which was lower than the average radiologists9 MAE of 3.471. The model achieved a precision of 0.69 [0.65, 0.74] and an F1 score of 0.67 [0.62, 0.71], which was significantly superior to the average reader precision of 0.68 [0.65, 0.71] and F1 score of 0.65 [0.63, 0.67]. The model demonstrated a sensitivity of 0.69 [95% CI: 0.65, 0.73] and specificity of 0.83 [95% CI: 0.81, 0.85], which was comparable to the performance of the three human readers, who had an average sensitivity of 0.71 [95% CI: 0.69, 0.73] and specificity of 0.84 [95% CI: 0.83, 0.85]. Conclusion: The AI model provided explainable results and performed at par with human readers in calculating CT severity scores from the chest CT scans of patients affected with COVID-19. The model had a lower MAE than that of the radiologists, indicating that the CTSS calculated by the AI was very close in absolute value to the CTSS determined by the reference standard.
Background: China witnessed a surge of Omicron infections after abandoning zero COVID strategies on December 7, 2022. The authorities report very sparse deaths based on very restricted criteria, but massive deaths are speculated. Methods: We aimed to estimate the COVID-19 fatalities in Mainland China until summer 2023 using the experiences of Hong Kong and of South Korea in 2022 as prototypes. Both these locations experienced massive Omicron waves after having had very few SARS-CoV-2 infections during 2020-2021. We estimated age-stratified infection fatality rates (IFRs) in Hong Kong and South Korea during 2022 and extrapolated to the population age structure of Mainland China. We also accounted separately for deaths of residents in long-term care facilities, which were prominent in Hong Kong. Results: IFR estimates in non-elderly strata were modestly higher in Hong Kong than South Korea and projected 987,455 and 811,571 maximal COVID-19 deaths, respectively, if the entire China population was infected. Expected COVID-19 deaths in Mainland China until summer 2023 ranged from 64,573 to 691,219 assuming 25-70% of the non-elderly population being infected and variable protection of elderly (from none to three-quarter reduction in fatalities). The main analysis (45% of non-elderly population infected and fatality impact among elderly reduced by half) estimated 199,223-249,094 COVID-19 deaths until summer 2023. Large uncertainties exist regarding potential changes in dominant variant, health system strain, and impact on non-COVID-19 deaths. Conclusions: The most critical factor that can affect total COVID-19 fatalities in China is the extent to which the elderly can be protected.
Introduction: The COVID 19 pandemic was highlighted by a rise in hospital admissions secondary to respiratory decompensation. This was accompanied by an increase in ICU admissions, endotracheal intubation and mechanical ventilation. As a consequence, tracheostomies became essential in preventing complications of prolonged intubation and to facilitate weaning from sedation and mechanical ventilation. With the lack of international consensus on tracheostomy technique and optimal timing, we present our experience with 377 percutaneous tracheostomies performed on critically ill COVID 19 patients. Objective: To report the outcomes of critically ill patients with COVID 19 who underwent percutaneous tracheostomy during a period of 24 months. Methods: A retrospective single-center electronic chart review was performed on all ICU patients who underwent percutaneous tracheostomy after respiratory failure secondary to COVID 19 between March 2020 to March 2022. Results: A total of 377 percutaneous tracheostomies were performed. The mean duration between intubation and percutaneous tracheostomy was 17.4 days (3 to 61). The study included 222 males (59%) and 155 females (41%). The mean age of patients was 56.2 years (17-94), with a mean BMI was 31.3 (14 to 68). The commonest comorbidities among patients were diabetes mellitus (50%) and hypertension (48%). Complications were encountered in 85 cases (23%), with the commonest overall complication being minor bleeding. 203 patients (54%) were weaned from sedation. The mean duration between tracheostomy and weaning from sedation was 7.5 days (1 to 47 days). 156 patients (41%) were weaned from MV. The mean duration between tracheostomy and weaning from MV was 12.9 days (1 to 58 days). There was a total of 236 (63%) deaths reported during the period of this study. No deaths were attributable to the surgical procedure. Conclusion: Percutaneous tracheostomy can be safely performed in patients with COVID 19. With lack of conclusive objective data regarding the optimal timing for tracheostomy, we recommend that tracheostomy be performed as soon as possible after the 7th day endotracheal intubation. Key Words: Percutaneous tracheostomy, COVID 19, Critically ill, ICU
Importance: Antenatal care provides unique opportunities to assess SARS-CoV-2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. Objective: Estimate seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid (anti-N) IgG) among pregnant people, and evaluate transplacental transfer efficiency. Design: Seroprevalence study: cross-sectional SARS-CoV-2 antibody screening among pregnant people December 9, 2020-June 19, 2021. Cohort study: Pregnant people screened anti-N IgG+ by Abbott Architect chemiluminescent immunoassay in seroprevalence study or identified through medical records with RT-PCR+ or antigen positive results enrolled in a prospective cohort December 9, 2020-June 30, 2022 to longitudinally measure anti-N IgG responses. We collected cord blood and assessed transplacental transfer of maternally-derived anti-N antibodies. Setting: Three hospitals and 14 affiliated clinics providing antenatal and delivery care, Seattle, Washington metropolitan area. Participants: Seroprevalence study: pregnant people were screened for SAR-CoV-2 anti-N IgG during routine care. Cohort study: Pregnant people with evidence of prior SARS-CoV-2 infection (screened anti-N IgG+ from seroprevalence study or identified with a RT-PCR+ or antigen positive result from medical records) were enrolled in a cohort study to longitudinally measure anti-N IgG responses. Exposure(s) (for observational studies): COVID-19 diagnosis, symptoms, and disease severity. Main Outcome(s) and Measure(s): Presence and durability of SARS-CoV-2 anti-N IgG, transplacental transfer of maternally-derived anti-N IgG. Results: Of 1289 pregnant people screened in the seroprevalence study, 5% (65) tested SARS-CoV-2 anti-N IgG+, including 39 (60%) without prior RT-PCR+ or antigen positive results and 53 (82%) without symptoms. Among 89 participants enrolled in the cohort study, 73 (82%) had anti-N IgG+ results during pregnancy. Among 49 participants with delivery samples 33 (67%) were anti-N IgG negative by delivery. Of 24 remaining anti-N IgG+ at delivery with paired cord blood samples, 12 (50%) had efficient transplacental anti-N IgG antibody transfer. Median time from first anti-N IgG to below positive antibody threshold was 17 weeks and did not differ by prior RT-PCR+ or antigen positive status. Conclusions and Relevance: Maternally-derived SARS-CoV-2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants.
Introduction: Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to not unstudied kinetics of the immune response after booster vaccinations. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. Patients and Methods: In 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. Results: IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2). Conclusion: Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.
101-PGC-005 for the Treatment of COVID-19 - Condition: COVID-19
Interventions: Drug: 101-PGC-005; Drug: Dexamethasone
Sponsor: 101 Therapeutics
Recruiting
A Clinical Study to Assess Preliminary Efficacy, Safety and Tolerability of HH-120 Nasal Spray in COVID-19 Patients - Condition: Coronavirus Disease 2019(COVID-19)
Intervention: Biological: HH-120 Nasal Spray
Sponsor: Beijing Ditan Hospital
Recruiting
COVID-19 Booster Study in Healthy Adults in Australia - Condition: COVID-19
Interventions: Biological: Bivalent Moderna; Biological: Novavax
Sponsors: Murdoch Childrens Research Institute; Coalition for Epidemic Preparedness Innovations; The Peter Doherty Institute for Infection and Immunity
Not yet recruiting
Effect of N-Acetylcysteine on Neutrophil Lymphocyte Ratio And Length of Stay In COVID-19 Patients - Condition: COVID-19
Intervention: Drug: N-acetyl cysteine
Sponsor: Universitas Sebelas Maret
Completed
Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations - Condition: COVID-19
Intervention: Drug: SA58 Nasal Spray
Sponsor: Sinovac Life Sciences Co., Ltd.
Recruiting
Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People - Condition: COVID-19
Interventions: Drug: SA58 Nasal Spray; Drug: Placebo
Sponsors: Sinovac Life Sciences Co., Ltd.; Beijing Ditan Hospital
Recruiting
Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
Efficacy and Safety of Ambervin® and Standard Therapy in Hospitalized Patients With COVID-19 - Condition: COVID-19
Interventions: Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate intramuscularly; Drug: Tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine succinate inhaled; Drug: Standard of care
Sponsor: Promomed, LLC
Completed
Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines - Condition: COVID-19
Interventions: Biological: CoronaVac/CoronaVac; Biological: CoronaVac/BNT162b2
Sponsor: Institut Pasteur de Tunis
Completed
Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above - Condition: COVID-19
Interventions: Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001; Biological: ZF2001
Sponsors: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.
Not yet recruiting
Study of GST-HG171/Ritonavir Compared With Placebo in Patients With Mild to Moderate COVID-19 - Condition: COVID-19 Pneumonia
Interventions: Drug: GST-HG171/Ritonavir; Drug: Placebo
Sponsor: Fujian Akeylink Biotechnology Co., Ltd.
Not yet recruiting
The COPE Study: Pilot Intervention to Improve Symptom Self-management and Coping in Adults With Post COVID-19 - Conditions: Post COVID-19 Condition; Post-COVID-19 Syndrome
Intervention: Behavioral: 6-Week Self-Management Group
Sponsor: University of Washington
Not yet recruiting
ICBT for Psychological Symptoms Related to the COVID-19 Pandemic Remaining After Societal Opening - Condition: Depression and Anxiety Symptoms Related to the COVID-19 Pandemic
Intervention: Behavioral: Internet-based Cognitive Behavioral Therapy
Sponsor: Linkoeping University
Not yet recruiting
ARVAC - A New Recombinant Coronavirus Disease 2019 (COVID-19) Vaccine - Condition: COVID-19 Vaccine
Intervention: Biological: ARVAC-CG vaccine (recombinant protein vaccine against SARS-CoV-2)
Sponsors: Laboratorio Pablo Cassara S.R.L.; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina
Active, not recruiting
The KIN-FAST Trial (KIN001 For Accelerated Symptoms Termination) in Non Hospitalized Patients Infected With SARS-CoV-2 - Condition: COVID-19
Interventions: Drug: KIN001; Drug: KIN001-Placebo
Sponsor: Kinarus AG
Recruiting
Ginkgolides and bilobalide for treatment of Alzheimer’s disease and COVID-19: potential mechanisms of action - Alzheimer’s disease (AD) is an irreversible degenerative illness of the central nervous system with characteristic histological alterations, known as amyloid plaques and neurofibrillary tangles (NFT). Aggregation of plaques and tangles in the brain induces neurotoxicity and synaptic dysfunction, eventually contributing to neuronal cell death and neurodegeneration. Recent studies have revealed that COVID-19 has a great impact on the development of AD, directly or indirectly, by facilitating the…
Identification of potent COVID-19 main protease inhibitors by loading of favipiravir on Mg12O12 and Zn12O12 nanoclusters: an in silico strategy for COVID-19 treatment - Pandemic new severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has increased throughout the world. There is no effective treatment against this virus until now. Since its appearance in Wuhan, China in December 2019, SARS-CoV-2 becomes the largest challenge the world is opposite today, including the discovery of an antiviral drug for this virus. Several viral proteins have been prioritized as SARS-CoV-2 antiviral drug targets, among them the papain-like protease (PLpro) and the…
Exploring the binding capacity of lactic acid bacteria derived bacteriocins against RBD of SARS-CoV-2 Omicron variant by molecular simulations - The changes in the SARS-CoV-2 genome have resulted in the emergence of new variants. Some of the variants have been classified as variants of concern (VOC). These strains have higher transmission rate and improved fitness. One of the prevalent were the Omicron variant. Unlike previous VOCs, the Omicron possesses fifteen mutations on the spike protein’s receptor binding domain (RBD). The modifications of spike protein’s key amino acid residues facilitate the virus’ binding capability against…
A bibliometric analysis of autophagy in lung diseases from 2012 to 2021 - CONCLUSION: The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and…
Impact of neutrophil extracellular traps on fluid properties, blood flow and complement activation - INTRODUCTION: The intravascular formation of neutrophil extracellular traps (NETs) is a trigger for coagulation and blood vessel occlusion. NETs are released from neutrophils as a response to strong inflammatory signals in the course of different diseases such as COVID-19, cancer or antiphospholipid syndrome. NETs are composed of large, chromosomal DNA fibers decorated with a variety of proteins such as histones. Previous research suggested a close mechanistic crosstalk between NETs and the…
Investigating Derivatives of Tanshinone IIA Sulfonate Sodium and Chloroxine for Their Inhibition Activities against the SARS-CoV-2 Papain-like Protease - SARS-CoV-2 has caused a global pandemic of COVID-19, posing a huge threat to public health. The SARS-CoV-2 papain-like cysteine protease (PLpro) plays a significant role in virus replication and host immune regulation, which is a promising antiviral drug target. Several potential inhibitors have been identified in vitro. However, the detailed mechanism of action and structure-activity relationship require further studies. Here, we investigated the structure-activity relationships of the series…
One-step synthesis of triethanolamine-capped Pt nanoparticle for colorimetric and electrochemiluminescent immunoassay of SARS-CoV spike proteins - Platinum nanoparticles (PtNPs) have been attracted worldwide attention due to their versatile application potentials, especially in the catalyst and sensing fields. Herein, a facile synthetic method of triethanolamine (TEOA)-capped PtNPs (TEOA@PtNP) for electrochemiluminescent (ECL) and colorimetric immunoassay of SARS-CoV spike proteins (SARS-CoV S-protein, a target detection model) is developed. Monodisperse PtNPs with an average diameter of 2.2 nm are prepared by a one-step hydrothermal…
Virus-like particle - mediated delivery of the RIG-I agonist M8 induces a type I interferon response and protects cells against viral infection - Virus-Like Particles (VLPs) are nanostructures that share conformation and self-assembly properties with viruses, but lack a viral genome and therefore the infectious capacity. In this study, we produced VLPs by co-expression of VSV glycoprotein (VSV-G) and HIV structural proteins (Gag, Pol) that incorporated a strong sequence-optimized 5’ppp-RNA RIG-I agonist, termed M8. Treatment of target cells with VLPs-M8 generated an antiviral state that conferred resistance against multiple viruses….
Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations - Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA…
Molecular Docking and Dynamic Simulation Revealed the Potential Inhibitory Activity of Opioid Compounds Targeting the Main Protease of SARS-CoV-2 - Opioids are a class of chemicals, naturally occurring in the opium poppy plant, and act on the brain to cause a range of impacts, notably analgesic and anti-inflammatory actions. Moreover, an overview was taken in consideration for SARS-CoV-2 incidence and complications, as well as the medicinal uses of opioids were discussed being a safe analgesic and anti-inflammatory drug in a specific dose. Also, our article focused on utilization of opioids in the medication of SARS-CoV-2. Therefore, the…
Inhibitory effects of fucoidan from Laminaria japonica against some pathogenic bacteria and SARS-CoV-2 depend on its large molecular weight - Fucoidan is a highly sulfated polysaccharide with a wide range of bioactivities, including anti-pathogenic activity. However, the relationship between structure and activity of fucoidan in inhibiting pathogen infections remains unclear. Here, different-molecular-weight fucoidans were prepared by photocatalytic degradation followed by membrane ultrafiltration, and their chemical structures and anti-pathogenic microbiota activity were compared. Results showed that photocatalytic degradation could…
Major royal jelly proteins elicited suppression of SARS-CoV-2 entry and replication with halting lung injury - For reasons of high transmissibility and virulence, Alpha (UK, B.1.1.7) and Beta (South African, B.1.351) SARS-CoV-2 variants are classified with other types as variants of concern. Here we report on the influence of royal jelly (RJ) protein fraction (PF)(50) (major RJ protein 2 and its isoform X1) on the entry of these variants into the ACE2-human embryonic kidney (HEK) 293 cells using the lentiviral system. The efficiency of PF(50) on SARS-CoV-2 replication (RNA-dependent RNA polymerase “RdRp”…
Identification and quantitative analysis of bioactive components from Potentilla kleiniana Wight et Arn with anti HIV-1 proteases activity - Potentilla kleiniana Wight et Arn(PK, ‘Wu Pi Feng’ in Chinese) was recorded as Miao ethnic medicine for treatment of fever, cough, ulcer, and erysipelas for thousands years. This study aimed to evaluate the antiviral activity of four PK extracts and seven compounds by using HIV-1 protease (HIV-1 PR). In addition, Ultra-High Performance Liquid Chromatography and High Resolution Mass Spectrometry (UPLC-HRMS) was employed to identify the bioactive components. The toxicity assessment of the extracts…
Targeting SARS-CoV-2 by synthetic dual-acting thiol compounds that inhibit Spike/ACE2 interaction and viral protein production - The SARS-CoV-2 life cycle is strictly dependent on the environmental redox state that influences both virus entry and replication. A reducing environment impairs the binding of the spike protein (S) to the angiotensin-converting enzyme 2 receptor (ACE2), while a highly oxidizing environment is thought to favor S interaction with ACE2. Moreover, SARS-CoV-2 interferes with redox homeostasis in infected cells to promote the oxidative folding of its own proteins. Here we demonstrate that synthetic…
Cell cycle block by p53 activation reduces SARS-CoV-2 release in infected alveolar basal epithelial A549-hACE2 cells - SARS-CoV viruses have been shown to downregulate cellular events that control antiviral defenses. They adopt several strategies to silence p53, key molecule for cell homeostasis and immune control, indicating that p53 has a central role in controlling their proliferation in the host. Specific actions are the stabilization of its inhibitor, MDM2, and the interference with its transcriptional activity. The aim of our work was to evaluate a new approach against SARS-CoV-2 by using MDM2 inhibitors…