scholarly journals Advances on Greener Asymmetric Synthesis of Antiviral Drugs via Organocatalysis

2021 ◽  
Vol 14 (11) ◽  
pp. 1125
Author(s):  
Everton M. da Silva ◽  
Hérika D. A. Vidal ◽  
Arlene G. Corrêa
Keyword(s):  
Pharmaceutical Industry ◽  
Antiviral Activity ◽  
Asymmetric Synthesis ◽  
High Mortality ◽  
Viral Infections ◽  
Mortality Rates ◽  
Chiral Drugs ◽  
Stereogenic Centers ◽  
Synthetic Routes ◽  
New Compounds

Viral infections cause many severe human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

scholarly journals Advances on Greener Asymmetric Synthesis of Antiviral Drugs via Organocatalysis

2021 ◽  
Author(s):  
Arlene Gonçalves Corrêa ◽  
Everton Machado da Silva ◽  
Herika Danielle Almeida Vidal
Keyword(s):  
Pharmaceutical Industry ◽  
Antiviral Activity ◽  
Asymmetric Synthesis ◽  
High Mortality ◽  
Viral Infections ◽  
Mortality Rates ◽  
Chiral Drugs ◽  
Stereogenic Centers ◽  
Synthetic Routes ◽  
New Compounds

Viral infections inflict many serious human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

scholarly journals Antibiotic-Resistant Bacteria in Green Turtle (Chelonia mydas) Rearing Seawater

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1841
Author(s):  
Thanaporn Chuen-Im ◽  
Korapan Sawetsuwannakun ◽  
Pimmnapar Neesanant ◽  
Nakarin Kitkumthorn
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infection ◽  
High Mortality ◽  
Mortality Rates ◽  
Sea Turtle ◽  
Resistant Isolate ◽  
Resistant Bacteria ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Increased Risk

Antibiotic resistance of microorganisms is a serious health problem for both humans and animals. Infection of these bacteria may result in therapy failure, leading to high mortality rates. During an early intervention program process, the Sea Turtle Conservation Center of Thailand (STCCT) has faced high mortality rates due to bacterial infection. Previously, investigation of juvenile turtle carcasses found etiological agents in tissue lesions. Further determination of sea water in the turtle holding tanks revealed a prevalence of these causative agents in water samples, implying association of bacterial isolates in rearing water and infection in captive turtles. In this study, we examined the antibiotic resistance of bacteria in seawater from the turtle holding tank for a management plan of juvenile turtles with bacterial infection. The examination was carried out in three periods: 2015 to 2016, 2018, and 2019. The highest isolate numbers were resistant to beta-lactam, whilst low aminoglycoside resistance rates were observed. No gentamicin-resistant isolate was detected. Seventy-nine isolates (71.17%) were resistant to at least one antibiotic. Consideration of resistant bacterial and antibiotic numbers over three sampling periods indicated increased risk of antibiotic-resistant bacteria to sea turtle health. Essentially, this study emphasizes the importance of antibiotic-resistant bacterial assessment in rearing seawater for sea turtle husbandry.

scholarly journals Identification of Feline Interferon Regulatory Factor 1 as an Efficient Antiviral Factor against the Replication of Feline Calicivirus and Other Feline Viruses

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yongxiang Liu ◽  
Xiaoxiao Liu ◽  
Hongtao Kang ◽  
Xiaoliang Hu ◽  
Jiasen Liu ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Viral Infections ◽  
Interferon Regulatory Factor ◽  
Feline Calicivirus ◽  
Type I ◽  
Norwalk Virus ◽  
Regulatory Factor ◽  
Feline Panleukopenia Virus ◽  
Protein Levels ◽  
Interferon Regulatory Factor 1

Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed. Further, we found that IRF1 was localized in the nucleus and efficiently activated IFN-β and the ISRE promoter. IRF1 can trigger the production of endogenous interferon and the expression of ISGs, suggesting that IRF1 can positively regulate IFN signalling. Importantly, the mRNA and protein levels of IRF1 were reduced upon FCV infection, which may be a new strategy for FCV to evade the innate immune system. Finally, the antiviral activity of IRF1 against feline panleukopenia virus, feline herpesvirus, and feline infectious peritonitis virus was demonstrated. These data indicate that feline IRF1 plays an important role in regulating the host type I IFN response and inhibiting feline viral infections.

scholarly journals Molecular Insights into the Fungus-Specific Serine/Threonine Protein Phosphatase Z1 in Candida albicans

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Emily Chen ◽  
Meng S. Choy ◽  
Katalin Petrényi ◽  
Zoltán Kónya ◽  
Ferenc Erdődi ◽  
...  
Keyword(s):  
Candida Albicans ◽  
High Mortality ◽  
Protein Phosphatase ◽  
Cyclic Peptide ◽  
Fungal Infections ◽  
The United States ◽  
Mortality Rates ◽  
Regulatory Proteins ◽  
Structural Elements ◽  
Novel Targets

ABSTRACT The opportunistic pathogen Candida is one of the most common causes of nosocomial bloodstream infections. Because candidemia is associated with high mortality rates and because the incidences of multidrug-resistant Candida are increasing, efforts to identify novel targets for the development of potent antifungals are warranted. Here, we describe the structure and function of the first member of a family of protein phosphatases that is specific to fungi, protein phosphatase Z1 (PPZ1) from Candida albicans . We show that PPZ1 not only is active but also is as susceptible to inhibition by the cyclic peptide inhibitor microcystin-LR as its most similar human homolog, protein phosphatase 1α (PP1α [GLC7 in the yeast Saccharomyces cerevisiae ]). Unexpectedly, we also discovered that, despite its 66% sequence identity to PP1α, the catalytic domain of PPZ1 contains novel structural elements that are not present in PP1α. We then used activity and pulldown assays to show that these structural differences block a large subset of PP1/GLC7 regulatory proteins from effectively binding PPZ1, demonstrating that PPZ1 does not compete with GLC7 for its regulatory proteins. Equally important, these unique structural elements provide new pockets suitable for the development of PPZ1-specific inhibitors. Together, these studies not only reveal why PPZ1 does not negatively impact GLC7 activity in vivo but also demonstrate that the family of fungus-specific phosphatases—especially PPZ1 from C. albicans —are highly suitable targets for the development of novel drugs that specifically target C. albicans without cross-reacting with human phosphatases. IMPORTANCE Candida albicans is a medically important human pathogen that is the most common cause of fungal infections in humans. In particular, approximately 46,000 cases of health care-associated candidiasis occur each year in the United States. Because these infections are associated with high mortality rates and because multiple species of Candida are becoming increasingly resistant to antifungals, there are increasing efforts to identify novel targets that are essential for C. albicans virulence. Here we use structural and biochemical approaches to elucidate how a member of a fungus-specific family of enzymes, serine/threonine phosphatase PPZ1, functions in C. albicans . We discovered multiple unique features of PPZ1 that explain why it does not cross-react with, and in turn compete for, PP1-specific regulators, a long-standing question in the field. Most importantly, however, these unique features identified PPZ1 as a potential target for the development of novel antifungal therapeutics that will provide new, safe, and potent treatments for candidiasis in humans.

scholarly journals Asymmetric synthesis of host-directed inhibitors of myxoviruses

2013 ◽  
Vol 9 ◽  
pp. 197-203 ◽  
Author(s):  
Terry W Moore ◽  
Kasinath Sana ◽  
Dan Yan ◽  
Pahk Thepchatri ◽  
John M Ndungu ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Asymmetric Synthesis ◽  
High Throughput ◽  
High Throughput Screening ◽  
Aqueous Solubility ◽  
Influenza Viruses ◽  
Lead Compound ◽  
Synthetic Strategy ◽  
Aqueous Solubilities ◽  
Nanomolar Range

High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC50 values in the low nanomolar range) and much improved aqueous solubilities relative to that of 1. Additionally, we have devised a robust synthetic strategy for preparing 1 and congeners in an enantio-enriched fashion, which has allowed us to demonstrate that the (S)-enantiomers are generally 7- to 110-fold more potent than the corresponding (R)-isomers.

scholarly journals How should an IACUC handle high mortality rates?

Lab Animal ◽  
2016 ◽  
Vol 45 (10) ◽  
pp. 355-355
Author(s):  
Jerald Silverman
Keyword(s):  
High Mortality ◽  
Mortality Rates

scholarly journals The nanocomposite fullerol reduces oxidative stress, pulmonary injury, and mortality in a rat model of acute lung injury

2021 ◽  
Author(s):  
Rosária Aires ◽  
Ildernandes Vieira-Alves ◽  
Leda Maria Coimbra-Campos ◽  
Marina Ladeira ◽  
Teresa Socarras ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
High Mortality ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Mortality Rates ◽  
Kaplan Meier ◽  
Pulmonary Damage

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10 to 10 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

Sign in / Sign up

Export Citation Format

Share Document