Biosafety and Health最新文献

The coronavirus disease of 2019 (COVID-19), a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can result in severe health complications. In addition to physical preventative measures, pharmaceutical intervention is also crucial. Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS-CoV-2 and other coronaviruses. In this study, we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels, as well as molecular separation and characterization, to screen and identify natural products with antiviral activity. Using this workflow, we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods. We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS-CoV-2 infection and receptor binding domain - human angiotensin-converting enzyme 2 (RBD-hACE2) binding in vitro. Following charge- and size-based characterization of the active compounds through filtration and chromatographic fractionation, mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition. Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID-19 and other diseases.

Worldwide, infections caused by drug-resistant pathogens constitute a significant challenge threatening therapeutic efforts. According to the World Health Organization (WHO), antimicrobial resistance (AMR) ranks among the top 10 global public health threats. Organisms with a high rate of multiple host adaptivity, significant genetic diversity (multiple lineages), high virulence factors, and genetic exchange have been isolated from various sources (humans, animals, and the environment) even without exposure to prior antibiotics. Till now, the source of AMR and how resistant clones are selected in the environment remain largely elusive, and potential anthropogenic transmission has been reported in different studies. Various drug-resistant pathogens, lineages, resistant clones, outbreak clusters, plasmid replicates, and genes that play a critical role in resistance dissemination have been identified. Maintenance of certain multidrug-resistant (MDR) determinants has also been shown to enhance or support the propagation of MDR. So far, significant advances have been made in understanding the burden of AMR. However, overcoming AMR requires a holistic approach, as there is no single approach with sufficient precision to curb the threat. While strengthening AMR surveillance efforts is essential, as we have shown, there is also a need to intensify efforts to strengthen therapeutic interventions, especially in priority regions such as Africa. Herein, we discussed the burden of AMR and the dissemination of AMR in humans, animals, and the environment (non-medical drivers). We further delved into the big questions on Africa and discussed how therapeutic interventions involving vaccines and other viable biomaterials could be pivotal in reducing the burden of AMR to the barest minimum.

The real-time reverse transcription-polymerase chain reaction (RT-PCR) test is the gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection. Proper specimen collection and obtaining a sufficient specimen are the most essential steps for laboratory diagnosis. The nasopharyngeal (NP) swab is recommended as the reference collection method. However, NP swab collection is invasive and uncomfortable for patients and poses some risk to healthcare workers. This study aimed to compare the efficacy of SARS-CoV-2 RNA detection from surgical masks with the NP swab method using RT-PCR testing. Of 269 patients, RT-PCR RNA from NP swabs was detected among 82 patients (30.5%) and was undetected among 187 patients (69.5%). All patients were tested for SARS-CoV-2 RNA from surgical masks. SARS-CoV-2 RNA was detected in 25/82 (30.5%) surgical mask filters, while undetected among 57 (69.5%). For the surgical mask with an average use time of 7.05 h, the sensitivity was 30.5%, the specificity was 100.0%, with positive predictive value of 100.0% and negative predictive value of 76.2%. Therefore, surgical masks could be an alternative non-invasive specimen source for SARS-CoV-2 RT-PCR testing. The results of our study suggest that the test could be employed after wearing surgical masks for at least 8-12 h, with increased sensitivity when used for more than 12 h.

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Beijing remain elusive. SARS-CoV-2-positive children admitted to the intensive care unit (ICU) with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis-based multiplex PCR from December 12, 2022, to January 24, 2023. The SARS-CoV-2 sub-variants were identified using next-generation sequencing. Plasma was positive for two (positive; P), one (suspicious; S), or no (negative; N) SARS-CoV-2 genes were classified as plasmatic RNA-positive (RNAemia; P + S) or without RNAemia (N). Clinical and laboratory data of the enrolled cases were then collected and analyzed. The 34 enrolled children included 26 males and 24 younger than three years. All were negative for other respiratory pathogens. BF.7.14 (18/29) was the predominant subvariant. Viral loads in respiratory specimens, hours from symptom onset to the first respiratory specimen collection (time-variable), with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs. N and RNAemia vs. without RNAemia group. Among most cases, the T lymphocyte ratios decreased, while the cytokine level and the B lymphocyte ratio increased. The time variables were 2.22 ± 2.05 and 4.00 ± 2.49 days in BF.7.14 and BA.5.2 infections, respectively. In conclusion, SARS-CoV-2 was more likely to cause severe infections among males aged ≤ 3 years old with comorbidities during the SARS-CoV-2 outbreak in Beijing, while RNAemia is more common in children at the early stage of severe BF.7.14 infections, and most had high cytokine levels and B-cell activation.

Antimicrobial resistance (AMR) is a growing global threat, especially in low- and middle-income countries (LMICs), causing prolonged illnesses, heightened antimicrobial use, increased healthcare expenses, and avoidable deaths. If not tackled, AMR could force 24 million people into severe poverty by 2030 and hinder progress on Sustainable Development Goals (SDGs). AMR spreads through interconnected ecosystems, with humans, animals, and the environment serving as reservoirs. Pharmaceutical wastewater, loaded with antibiotics and resistance genes, poses a significant environmental risk, mainly due to inadequate treatment and irresponsible disposal. The pharmaceutical industry is a notable contributor to environmental antibiotic pollution, with varying effluent management practices. Contaminated pharmaceutical wastewater discharge harms water sources and ecosystems. Urgent collaborative efforts are needed across policymakers, regulators, manufacturers, researchers, civil society, and communities, adopting a One Health approach to curb AMR's spread. Developing global standards for pharmaceutical effluent antibiotic residues, effective treatment methods, and improved diagnostics are vital in addressing AMR's environmental impact while safeguarding public health and the environment. National action plans should encompass comprehensive strategies to combat AMR. Preserving antibiotic efficacy and ensuring sustainable production require a united front from all stakeholders.

Understanding how human leukocyte antigen (HLA) polymorphism affects both the susceptibility and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will help to identify individuals at higher risk to better manage and prioritize vaccination at the clinical level and explain the differences in epidemic trends in different regions at the epidemiological level. This study compared the frequencies of HLA class I alleles (HLA-A, B) in 214 coronavirus disease 2019 (COVID-19) patients with different disease severity and 35 healthy controls and analyzed the correlations between specific HLA alleles and disease severity and T cell memory. The results showed no significant difference in HLA allele frequencies between COVID-19 patients and healthy controls (P > 0.05). The allele HLA-B*13:02 was significantly correlated with the disease severity of COVID-19 patients (P = 0.006). After adjustment for age and disease severity, the T cell responses of COVID-19 convalescents with the allele HLA-B*40:01 may be lower at six months (P = 0.044) and 12 months (P = 0.069). Moreover, these results may be due to their rare peptide anchors by analyzing the binding peptide motifs of these HLA alleles. The study may be valuable for investigating the potential association of specific HLA alleles with SARS-CoV-2 infection.

Enteroviruses (EVs) are human pathogens commonly observed in children aged 0–5 years and adults. EV infections usually cause the common cold and hand-foot-and-mouth disease; however, more severe infections can result in multiorgan complications, such as polio, aseptic meningitis, and myocarditis. The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood, but accumulating evidence points to two enterovirus proteases, 2A^pro and 3C^pro, as the key players in pathogenesis. The 2A^pro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication. It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2A^pro-mediated cleavage of dystrophin in cardiomyocytes, indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases. Therefore, studies of 2A^pro could reveal additional substrates that may be associated with specific diseases. Here, we discuss the genetic and structural properties of 2A^pro and review how the protease antagonizes innate immune responses to promote viral replication, as well as novel substrates and mechanisms for 2A^pro. We also summarize the current approaches for identifying the substrates of 2A^pro to discover novel mechanisms relating to certain diseases.