Antibacterial, Antibiofilm, and Antioxidant Activity of 15 Different Plant-Based Natural Compounds in Comparison with Ciprofloxacin and Gentamicin.

Plant-based natural compounds (PBCs) are comparatively explored in this study to identify the most effective and safe antibacterial agent/s against six World Health Organization concern pathogens. Based on a contained systematic review, 11 of the most potent PBCs as antibacterial agents are included in this study. The antibacterial and antibiofilm efficacy of the included PBCs are compared with each other as well as common antibiotics (ciprofloxacin and gentamicin). The whole plants of two different strains of Cannabis sativa are extracted to compare the results with sourced ultrapure components. Out of 15 PBCs, tetrahydrocannabinol, cannabidiol, cinnamaldehyde, and carvacrol show promising antibacterial and antibiofilm efficacy. The most common antibacterial mechanisms are explored, and all of our selected PBCs utilize the same pathway for their antibacterial effects. They mostly target the bacterial cell membrane in the initial step rather than the other mechanisms. Reactive oxygen species production and targeting [Fe-S] centres in the respiratory enzymes are not found to be significant, which could be part of the explanation as to why they are not toxic to eukaryotic cells. Toxicity and antioxidant tests show that they are not only nontoxic but also have antioxidant properties in Caenorhabditis elegans as an animal model.

Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant: A Systematic Review and Meta-Analysis of Clinical Studies.

The high transmissibility, mortality, and morbidity rate of the SARS-CoV-2 Delta (B.1.617.2) variant have raised concerns regarding vaccine effectiveness (VE). To address this issue, all publications relevant to the effectiveness of vaccines against the Delta variant were searched in the Web of Science, Scopus, EMBASE, and Medline (via PubMed) databases up to 15 October 2021. A total of 15 studies (36 datasets) were included in the meta-analysis. After the first dose, the VE against the Delta variant for each vaccine was 0.567 (95% CI 0.520-0.613) for Pfizer-BioNTech, 0.72 (95% CI 0.589-0.822) for Moderna, 0.44 (95% CI 0.301-0.588) for AstraZeneca, and 0.138 (95% CI 0.076-0.237) for CoronaVac. Meta-analysis of 2,375,957 vaccinated cases showed that the Pfizer-BioNTech vaccine had the highest VE against the infection after the second dose, at 0.837 (95% CI 0.672-0.928), and third dose, at 0.972 (95% CI 0.96-0.978), as well as the highest VE for the prevention of severe infection or death, at 0.985 (95% CI 0.95-0.99), amongst all COVID-19 vaccines. The short-term effectiveness of vaccines, especially mRNA-based vaccines, for the prevention of the Delta variant infection, hospitalization, severe infection, and death is supported by this study. Limitations include a lack of long-term efficacy data, and under-reporting of COVID-19 infection cases in observational studies, which has the potential to falsely skew VE rates. Overall, this study supports the decisions by public health decision makers to promote the population vaccination rate to control the Delta variant infection and the emergence of further variants.

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.

Zinc and SARS­CoV­2: A molecular modeling study of Zn interactions with RNA­dependent RNA­polymerase and 3C­like proteinase enzymes.

RNA­dependent RNA­polymerase (RdRp) and 3C­like proteinase (3CLpro) are two main enzymes that play a key role in the replication of SARS­CoV­2. Zinc (Zn) has strong immunogenic properties and is known to bind to a number of proteins, modulating their activities. Zn also has a history of use in viral infection control. Thus, the present study models potential Zn binding to RdRp and the 3CLpro. Through molecular modeling, the Zn binding sites in the aforementioned two important enzymes of viral replication were found to be conserved between severe acute respiratory syndrome (SARS)­coronavirus (CoV) and SARS­CoV­2. The location of these sites may influence the enzymatic activity of 3CLpro and RdRp in coronavirus disease 2019 (COVID­19). Since Zn has established immune health benefits, is readily available, non­expensive and a safe food supplement, with the comparisons presented here between SARS­CoV and COVID­19, the present study proposes that Zn could help ameliorate the disease process of COVID­19 infection.

Comparison of influenza type A and B with COVID-19: A global systematic review and meta-analysis on clinical, laboratory and radiographic findings.

We compared clinical symptoms, laboratory findings, radiographic signs and outcomes of COVID-19 and influenza to identify unique features. Depending on the heterogeneity test, we used either random or fixed-effect models to analyse the appropriateness of the pooled results. Overall, 540 articles included in this study; 75,164 cases of COVID-19 (157 studies), 113,818 influenza type A (251 studies) and 9266 influenza type B patients (47 studies) were included. Runny nose, dyspnoea, sore throat and rhinorrhoea were less frequent symptoms in COVID-19 cases (14%, 15%, 11.5% and 9.5%, respectively) in comparison to influenza type A (70%, 45.5%, 49% and 44.5%, respectively) and type B (74%, 33%, 38% and 49%, respectively). Most of the patients with COVID-19 had abnormal chest radiology (84%, p < 0.001) in comparison to influenza type A (57%, p < 0.001) and B (33%, p < 0.001). The incubation period in COVID-19 (6.4 days estimated) was longer than influenza type A (3.4 days). Likewise, the duration of hospitalization in COVID-19 patients (14 days) was longer than influenza type A (6.5 days) and influenza type B (6.7 days). Case fatality rate of hospitalized patients in COVID-19 (6.5%, p < 0.001), influenza type A (6%, p < 0.001) and influenza type B was 3%(p < 0.001). The results showed that COVID-19 and influenza had many differences in clinical manifestations and radiographic findings. Due to the lack of effective medication or vaccine for COVID-19, timely detection of this viral infection and distinguishing from influenza are very important.

Comparison of confirmed COVID-19 with SARS and MERS cases - Clinical characteristics, laboratory findings, radiographic signs and outcomes: A systematic review and meta-analysis.

INTRODUCTION: Within this large-scale study, we compared clinical symptoms, laboratory findings, radiographic signs, and outcomes of COVID-19, SARS, and MERS to find unique features. METHOD: We searched all relevant literature published up to February 28, 2020. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Study has been registered in the PROSPERO database (ID 176106). RESULT: Overall 114 articles included in this study; 52 251 COVID-19 confirmed patients (20 studies), 10 037 SARS (51 studies), and 8139 MERS patients (43 studies) were included. The most common symptom was fever; COVID-19 (85.6%, P < .001), SARS (96%, P < .001), and MERS (74%, P < .001), respectively. Analysis showed that 84% of Covid-19 patients, 86% of SARS patients, and 74.7% of MERS patients had an abnormal chest X-ray. The mortality rate in COVID-19 (5.6%, P < .001) was lower than SARS (13%, P < .001) and MERS (35%, P < .001) between all confirmed patients. CONCLUSIONS: At the time of submission, the mortality rate in COVID-19 confirmed cases is lower than in SARS- and MERS-infected patients. Clinical outcomes and findings would be biased by reporting only confirmed cases, and this should be considered when interpreting the data.