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2021 ◽  
Vol 226 ◽  
pp. 113873
Alice Legru ◽  
Federica Verdirosa ◽  
Jean-François Hernandez ◽  
Giusy Tassone ◽  
Filomena Sannio ◽  

Virology ◽  
2021 ◽  
Vol 564 ◽  
pp. 33-38
Yining Wang ◽  
Pengfei Li ◽  
Kundan Solanki ◽  
Yang Li ◽  
Zhongren Ma ◽  

2021 ◽  
Matthias Götte ◽  
Calvin J. Gordon ◽  
Hery W. Lee ◽  
Egor P. Tchesnokov ◽  
Jason K. Perry ◽  

Remdesivir (RDV) is a direct antiviral agent that is approved in several countries for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RDV exhibits broad-spectrum antiviral activity against positive-sense RNA viruses, e.g., SARS-CoV-2 and hepatitis C virus (HCV) and non-segmented negative-sense RNA viruses, e.g., Nipah virus (NiV), while several segmented negative-sense RNA viruses such as influenza (Flu) virus or Crimean-Congo hemorrhagic fever virus (CCHFV) are not sensitive to the drug. The reasons for this apparent pattern are unknown. Here, we expressed and purified representative RNA-dependent RNA polymerases (RdRp) and studied three biochemical parameters that have been associated with the inhibitory effects of RDV-triphosphate (TP): (i) selective incorporation of the nucleotide substrate RDV-TP, (ii) the effect of the incorporated RDV-monophosphate (MP) on primer extension, and (iii) the effect of RDV-MP in the template during incorporation of the complementary UTP. The results of this study revealed a strong correlation between antiviral effects and efficient incorporation of RDV-TP. Delayed chain-termination is heterogeneous and usually inefficient at higher NTP concentrations. In contrast, template-dependent inhibition of UTP incorporation opposite the embedded RDV-MP is seen with all polymerases. Molecular modeling suggests a steric conflict between the 1′-cyano group of RDV-MP and conserved residues of RdRp motif F. We conclude that future efforts in the development of nucleotide analogues with a broader spectrum of antiviral activities should focus on improving rates of incorporation while capitalizing on the inhibitory effects of a bulky 1′-modification.

2021 ◽  
Vol 8 ◽  
Emma Cebrian ◽  
Laura Tamburello ◽  
Jana Verdura ◽  
Giuseppe Guarnieri ◽  
Alba Medrano ◽  

Canopy-forming macroalgae play a crucial role in coastal primary production and nutrient cycling, providing food, shelter, nurseries, and habitat for many vertebrate and invertebrate species. However, macroalgal forests are in decline in various places and natural recovery is almost impossible when populations become locally extinct. Hence, active restoration emerges as the most promising strategy to rebuild disappeared forests. In this regard, significant efforts have been made by several EU institutions to research new restoration tools for shallow and mesophotic reef habitats (e.g., MERCES EU project, AFRIMED, and ROCPOP-life) and effective techniques have subsequently been proposed to promote self-sustaining populations. Recent research indicates that macroalgal forest recovery requires a broad spectrum of measures, ranging from mitigating human impacts to restoring the most degraded populations and habitats, and that the viability of large restoration actions is compromised by ongoing human pressures (e.g., pollution, overgrazing, and climate change). We propose a roadmap for Mediterranean macroalgal restoration to assist researchers and stakeholders in decision-making, considering the most effective methods in terms of cost and cost-effectiveness, and taking background environmental conditions and potential threats into account. Last, the challenges currently faced by the restoration of rocky coastal ecosystems under changing climate conditions are also discussed.

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Marin H. Kollef ◽  
Andrew F. Shorr ◽  
Matteo Bassetti ◽  
Jean-Francois Timsit ◽  
Scott T. Micek ◽  

AbstractSevere or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.

Bei Yue ◽  
Ruiyang Gao ◽  
Zhengtao Wang ◽  
Wei Dou

Irinotecan (CPT11) and its active metabolite ethyl-10-hydroxy-camptothecin (SN38) are broad-spectrum cytotoxic anticancer agents. Both cause cell death in rapidly dividing cells (e.g., cancer cells, epithelial cells, hematopoietic cells) and commensal bacteria. Therefore, CPT11 can induce a series of toxic side-effects, of which the most conspicuous is gastrointestinal toxicity (nausea, vomiting, diarrhea). Studies have shown that the gut microbiota modulates the host response to chemotherapeutic drugs. Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation. This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called “microbiota-host-irinotecan axis”. Also, we emphasize the utilization of bacterial β-glucuronidase-specific inhibitor, dietary interventions, probiotics and strain-engineered interventions as emergent microbiota-targeting strategies for the purpose of improving CPT11 chemotherapy efficiency and alleviating toxicity.

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 574
Natalia Castejón ◽  
Maroussia Parailloux ◽  
Aleksandra Izdebska ◽  
Ryszard Lobinski ◽  
Susana C. M. Fernandes

Until now, the red algae Gelidium sesquipedale has been primarily exploited for agar production, leaving an undervalued biomass. In this work, the use of eco-friendly approaches employing ultrasound-assisted extraction (UAE) and green solvents was investigated to valorize the algal minor compounds. The green methods used herein showed an attractive alternative to efficiently extract a broad spectrum of bioactive compounds in short extraction times (15 to 30 min vs. 8 h of the conventional method). Using the best UAE conditions, red seaweed extracts were characterized in terms of total phenolics (189.3 ± 11.7 mg GAE/100 g dw), flavonoids (310.7 ± 9.7 mg QE/100 g dw), mycosporine-like amino acids (MAAs) (Σ MAAs = 1271 mg/100 g dw), and phycobiliproteins (72.4 ± 0.5 mg/100 g dw). Additionally, produced algal extracts exhibited interesting antioxidant and anti-enzymatic activities for potential applications in medical and/or cosmetic products. Thus, this study provides the basis to reach a superior valorization of algal biomass by using alternative methods to extract biologically active compounds following eco-friendly approaches. Moreover, the strategies developed not only open new possibilities for the commercial use of Gelidium sesquipedale, but also for the valorization of different algae species since the techniques established can be easily adapted.

2021 ◽  
Vol In Press (In Press) ◽  
Seyed Alireza Fahimzad ◽  
Bahador Mirrahimi ◽  
Farideh Shiva ◽  
Niloofar Esfahanian ◽  
Seyyedeh Azam Mousavizadeh ◽  

Background: Surgical procedures may be complicated by post-surgical infections. This study investigates the role of administering perioperative narrow-spectrum antibiotic prophylaxis in preventing post-surgical infections as compared to routine broad-spectrum antibiotic usage in the surgical ward. Methods: Narrow-spectrum perioperative antibiotic prophylaxis, in accordance with CDC guidelines, was implemented in our hospital in October 2019. In this quasi-experimental study, all the children (one month to fifteen years old) who underwent surgery from April to September 2019 and had received broad-spectrum antibiotics for various durations, as well as those operated after the implementation of the perioperative narrow-spectrum antibiotic prophylaxis plan (October 2019 to March 2020) were enrolled. Surgical wound type (clean, clean/contaminated, contaminated, and dirty), type and site of the infection, and the patient’s age and sex were recorded. Cases with postoperative infections were followed up in the two groups during hospitalization and for 30 days (or 90 days if a prosthetic material was implanted) after discharge. The rate of post-surgical infections was compared between the two groups by the Mann-Whitney and Chi-squared tests. Results: In total, 4308 cases were enrolled in the first six months and 3650 in the second six months of the study. The rate of post-surgical infections in the first group was 31/4380 (23.7%) as compared to 22/3650 (20%) in the second group (P-value = 0.3365) Conclusions: There was no increase in the frequency of post-surgical infections after the implementation of the perioperative narrow-spectrum antibiotic prophylaxis protocol. Reducing the use of antibiotics before surgery shrinks costs and antibiotic resistance without any effect on the post-surgical infection rate.

Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3550
Gonzalo R. Quezada ◽  
Norman Toro ◽  
Jorge Saavedra ◽  
Pedro Robles ◽  
Iván Salazar ◽  

Polymers have interesting physicochemical characteristics such as charge density, functionalities, and molecular weight. Such attributes are of great importance for use in industrial purposes. Understanding how these characteristics are affected is still complex, but with the help of molecular dynamics (MD) and quantum calculations (QM), it is possible to understand the behavior of polymers at the molecular level with great consistency. This study was applied to polymers derived from polyacrylamide (PAM) due to its great use in various industries. The polymers studied include hydrolyzed polyacrylamide (HPAM), poly (2-acrylamido-2-methylpropanesulfonate) (PAMPS), polyacrylic acid (PAA), polyethylene oxide polymer (PEO), and guar gum polysaccharide (GUAR). Each one has different attributes, which help in understanding the effects on the polymer and the medium in which it is applied along a broad spectrum. The results include the conformation, diffusion, ion condensation, the structure of the water around the polymer, and interatomic polymer interactions. Such characteristics are important to selecting a polymer depending on the environment in which it is found and its purpose. The effect caused by salinity is particular to each polymer, where polymers with an explicit charge or polyelectrolytes are more susceptible to changes due to salinity, increasing their coiling and reducing their mobility in solution. This naturally reduces its ability to form polymeric bridges due to having a polymer with a smaller gyration radius. In contrast, neutral polymers are less affected in their structure, making them favorable in media with high ionic charges.

2021 ◽  
Pengfei Wang ◽  
Ryan G Casner ◽  
Manoj S Nair ◽  
Jian Yu ◽  
Yicheng Guo ◽  

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

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