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In this study, cotton fabrics based on zinc oxide nanoparticles in situ synthesis, acyclovir, nanochitosan, and clove oil were treated. The treated cotton fabrics were examined by FTIR, HR-TEM, FE-SEM, EDAX, and the surface roughness processing of FE-SEM images. The obtained characterization data emphasized the nano-size of nanocomposite with high homogeneity of particles in spherical shape as well as affirmed the deposition of nanocomposite onto the textile fibers with concluded that the deposition of nanocomposite was increased parallel with sonication time. Antimicrobial and antiviral activities of treated cotton fabrics were evaluated. Results revealed that treated cotton fabrics exhibited promising antibacterial activity toward Gram-positive higher than Gram-negative bacteria. Likewise, treated cotton fabrics are still effective as antibacterial after washing for 100 cycles. Moreover, treated cotton fabrics exhibited potential antifungal activity against Candida albicans, Aspergillus niger, and Aspergillus fumigatus. The antiviral activity significantly depended on the type of virus. The treated cotton fabrics showed antiviral activity against tested viral particles (HSV-1, Adeno, and CoxB2) with viral inhibition of 95.9, 76.4, and 86.9% respectively, while in the case of coated cotton textile with acyclovir, it only exhibited viral inhibition of 49.9, 41, and 22.3% respectively., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3' position. Monofatty acyl conjugates, 3'-O-tetradecanoyl (4a) (IC 50(VeroE6)  = 2.3 μM; IC 50(Calu3)  = 0.24 μM), 3'-O-4-oxatetradodecanoyl (4b) (IC 50(VeroE6)  = 2.0 μM; IC 50(Calu3)  = 0.18 μM), and 3'-O-(12-ethylthiododecanoyl) (4e) (IC 50(VeroE6)  = 2.4 μM; IC 50(Calu3)  = 0.25 μM) derivatives exhibited less activity than RDV (IC 50(VeroE6)  = 0.85 μM; IC 50(Calu3)  = 0.06 μM) in both VeroE6 and Calu3 cells. Difatty acylation led to a significant reduction in the antiviral activity of RDV (as shown in conjugates 5a and 5b) against SARS-CoV-2 when compared with monofatty acylation (3a-e and 4a-e). About 77.9% of 4c remained intact after 4 h incubation with human plasma while only 47% of parent RDV was observed at the 2 h time point. The results clearly indicate the effectiveness of fatty acylation to improve the half-life of RDV. The antiviral activities of a number of monofatty acyl conjugates of RDV, such as 3b, 3e, and 4b, were comparable with RDV against the Ebola trVLP system. Meanwhile, the corresponding physical mixtures of RDV and fatty acids 6a and 6b showed 1.6 to 2.2 times less antiviral activity than the corresponding conjugates, 4a and 4c, respectively, against SARS-CoV-2 in VeroE6 cells. A significant reduction in viral RNA synthesis was observed for selected compounds 3a and 4b consistent with the IC 50 results. These studies indicate the potential of these compounds as long-acting antiviral agents or prodrugs of RDV., Competing Interests: Declaration of competing interest The increasing prevalence of COVID-19 is a severe public health problem affecting people globally. COVID-19 is taking a devastating toll on human lives. Several existing drugs and potential drug candidates such as remdesivir (RDV) have been considered for repurposing as COVID-19 treatments. Our group has previously studied the impact of fatty acylation on the antiviral activity of different anti-HIV (human immunodeficiency virus) nucleoside drugs. The conjugates were more potent and less toxic than their parent nucleoside analogs, providing a much higher selectivity index. Furthermore, the conjugates significantly enhanced the cellular uptake versus the parent analogs and corresponding physical mixtures of fatty acids and nucleosides. Herein, we report the synthesis of fatty acyl derivatives of RDV and structural characterization of their antiviral activity against SARS-CoV-2 in VeroE6 cells and Calu3 cells. Five fatty acids, myristic acid, 12-azidododecanoic acid, 12-thioethyldodecanoic acid, 4-oxatetradecanoic acid, and palmitic acid were conjugated to RDV at its 2′-O- and 3′-O-position. Most monofatty acyl derivatives of RDV demonstrated IC(50) values against SARS-CoV-2 that were only slightly decreased relative to RDV. Against the EBOV trVLP and infectious EBOV, any of the monofatty acyl conjugates had IC(50)s similar to that of RDV. Overall, these data together indicate that RDV can be modified with fatty acids at positions 2′ or 3′, without demonstrating a significant loss of antiviral activity in cell culture against SARS-CoV-2 and EBOV. Future studies will determine if these modifications result in greater long-acting effect, bioavailability, and stability in animal models., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019 and rapidly spread to other provinces in China as well as other countries. In this study, 262 patients diagnosed with moderate to severe SARS-CoV-2 pneumonia in Wuhan, China, were analyzed. Data were compared between survivors and nonsurvivors. Of all the 262 patients, 23 (8.8%) patients died and 239 (91.2%) were discharged. The median age was 63.5 years and 46.9% of patients were male. The main complaints were fever (83.6%), cough (63.4%), and fatigue (49.2%) in the surviving group, while there were more complaints of dyspnea (39.1%) and shortness of breath (56.5%) in the nonsurviving group. The main comorbidities were hypertension (35.5%), diabetes mellitus (16.4%), and coronary artery disease (9.9%). Morbidity is higher in elderly patients with more comorbidities. Patients were mainly treated with nasal cannula (93.9%), while the nonsurviving group received more invasive mechanical ventilation (39.1%). Arbidol (80.9%), ribavirin (36.6%), oseltamivir (38.9%), interferon (16.4%), and ganciclovir (14.5%) were used for the antiviral treatment. In the nonsurviving group, the number of white blood cells (WBC) was significantly increased and lymphocytes were decreased, and lymphopenia was more common. The levels of aspartate transaminase (AST), brain natriuretic peptide (BNP), creatine kinase isoenzyme MB (CK-MB), lactate dehydrogenase (LDH), and C-reactive protein (CRP) were also significantly increased in the nonsurviving group. The adjusted hazard ratios (HRs) for association of known variables for all-cause mortality due to the coronavirus disease 2019 were 2.467 (95% confidence interval [CI], 1.007-6.044; p  = 0.048) for shortness of breath and 1.025 (95% CI, 1.001-1.049; p  = 0.042) for AST. Elderly patients with more comorbidities and complaints of dyspnea and shortness of breath had increased risk of death. Patients with lymphopenia and high levels of WBC, AST, BNP, CK-MB, LDH, and CRP may be more likely to deteriorate.

Objective: To investigate the clinical efficacy and short-term and long-term adverse reactions for different antiviral regiments for coronavirus disease 2019 (COVID-19) in Ningxia Hui Autonomous Region during hospitalization and follow-up in 3 months., Methods: A single-center retrospective study was conducted to enroll the COVID-19 patients in isolation ward of the only designated hospital to receive COVID-19 patients (the Fourth People's Hospital of Ningxia Hui Autonomous Region) when the authors were assigned by the Ningxia Health Commission as experts from January 20, 2020 to March 15, 2020. According to the antiviral regimen, the patients were divided into conventional antiviral group and unconventional antiviral group. The conventional antiviral group received α-interferon combined with Lopinavir/Ritonavir (LPV/R). The unconventional antiviral group was given α-interferon combined with LPV/R and Abidor or Ribavirin or Chloroquine. The patients were divided into mild (13 cases), ordinary (45 cases), severe (14 cases) and critical (1 case) types. The clinical data, length of hospital stay, the first 2019 novel coronavirus (2019-nCoV) nucleic acid negative recovery time, cost of hospitalization, 2019-nCoV nucleic acid positive reversal after 14 days of discharge, and the combination of hormones and antibiotics were collected. The differences in blood routine, liver function, blood lipid level and adverse reactions of antiviral drugs during hospitalization were compared between the two groups at 1, 3 and 7 days after admission and 1 and 3 months after discharge., Results: (1) General information: a total of 75 patients with confirmed COVID-19 were admitted, and 73 patients were eventually enrolled, including 47 cases in the conventional antiviral group and 26 cases in the unconventional antiviral group. Patients with different clinical classification were analyzed, the higher the clinical classification and the patients' age, the higher the proportion of primary diseases and the cost of treatment, and the longer the length of hospital stay. Compared with conventional antiviral group, in unconventional antiviral group the percentage of severe and critical patients were higher [34.6% (9/26) vs. 10.6% (5/47), 3.8% (1/26) vs. 0 (0/47)], the length of hospital stay (days: 16.1±5.6 vs. 11.6±3.3), first nucleic acid negative recovery time (days: 12.4±4.5 vs. 10.0±3.5) were longer, and hospitalization cost was higher [Yuan: 11 984.2 (9 000.6, 24 424.7) vs. 8 140.4 (6 715.7,9 707.7)], with statistically significant differences (all P < 0.05). There were no significant differences in gender, age, proportion of patients with primary diseases and nucleic acid positive reversal rate after 14 days of discharge between the unconventional and conventional antiviral groups (all P > 0.05). (2) Laboratory tests: during the hospitalization, white blood cell count (WBC), platelet count (PLT), total bilirubin (TBil) and three acyl glycerin (TG) levels were first increased and then reduced, lymphocyte count (LYM) was first decreased and then increased in two groups. In the unconventional antiviral group, WBC [(6.53±2.78)×10 9 /L], PLT [(250.77±96.12)×10 9 /L], and TG [(1.94±0.96) μmol/L] all reached their peak values at 7 days after admission. TBil peaked at 3 days after admission, which was (23.69±12.14) μmol/L, and LYM reached the peak 1 month after discharge, which was (1.82±0.50)×10 9 /L; however, there was no statistical significance among the above indicators between two groups. There were no statistically significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total cholesterol (TC) between the two groups at each time point. (3) The ratio of combined use of hormones in the non-antiviral group was significantly higher than that in the conventional antiviral group [26.9% (7/26) vs. 4.3% (2/47), P < 0.05]., Conclusions: Age and associated primary diseases are related to the severity of COVID-19 patients. Unconventional antiviral treatment regimens are mostly used for severe COVID-19 patients whose ucleic acid did not turn negative for a long time. Individual antiviral therapy can be used based on the patients' response and tolerance to drugs.

A lipophilic dideoxynucleoside analogue, 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), was expected to be effective against AIDS-related dementia. In this study, we tested the effect of 6-Cl-ddG on simian immunodeficiency virus (SIVmac239) replication in vitro and on acute infection of six rhesus monkeys (Macaca mulatta) with SIVmac239. This compound inhibited SIV-induced cytopathic effect in CEM x 174 cells and SIV replication in vitro with an ED50 value of 2.5 microM. A dose of 25 mg/kg 6-Cl-ddG was administered to three monkeys every 8 h for 10 days and an untreated group of three monkeys was injected with the solvent without drug. Although 6-Cl-ddG was not detected in the plasma, the metabolite ddG was maintained at a concentration of more than 3 microM for 8 h after administration. In the cerebrospinal fluid, the ddG concentration was 2 microM at 2 h after administration. SIV antigen (p27) and antibody appearance in the plasma were delayed for 5-8 days compared with the mock-treated group. The occurrence of lymphadenopathy in treated monkeys was delayed for 6 days compared with the mock-treated group. Signs of 6-Cl-ddG toxicity were minimal after the treatment. The results of this study provide further evidence that 6-Cl-ddG may act as a potent anti-human immunodeficiency virus agent in vivo.

To assess the therapeutic effects of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG), a lipophilic dideoxynucleoside analogue, three rhesus macaques chronically infected with simian immunodeficiency virus (SIVmac239) were subcutaneously administered 25 mg/kg of the drug every 8 hours for 2 weeks. In two of three animals, the viral RNA in plasma and the cell-associated viral load from peripheral blood mononuclear cells were markedly decreased and the number of CD4+ and CD8+ lymphocytes were increased after 6-Cl-ddG administration. The decrease of the virus copies was associated with a reciprocal increase in the number of CD4+ lymphocytes. Additionally, a limiting dilution assay revealed a marked decrease in the lymph node cell-associated virus titer during the treatment. However, in the third monkey, the baseline of the number of CD4+ and CD8+ lymphocytes was higher than that of the other monkeys; these numbers changed very little during the treatment. In this monkey, the plasma SIV RNA level was decreased at the first week and was the same as the pretreatment level at the second week of the 6-Cl-ddG administration. In all three treated monkeys, the number of SIV RNA copies in the cerebrospinal fluid also tended to decrease during the 6-Cl-ddG treatment.

The efficacy of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) was investigated in vivo by using a male ARC/AIDS rhesus macaque infected with simian immunodeficiency virus (SIVmac251/32H). He was administered subcutaneously 6-Cl-ddG (50 mg/kg B.W.) every 8 hr for 14 days when he showed clinical features of recurrent weight loss, severe diarrhea and neuropathy. The number of CD4+, CD8+ cells and total T cells increased rapidly after administration of 6-Cl-ddG and a high level was maintained for 2 months, but the B cell count decreased during the treatment. The antibody titer to SIV did not change significantly during or after the treatment, but the virus load in the plasma measured by RT-PCR dropped to one-third at the start of the 6-Cl-ddG treatment. Within 3 days after the start of 6-Cl-ddG administration, he began to show recovery in clinical signs including weight increase, and disappearance of diarrhea and neuropathy. These findings suggested that 6-Cl-ddG was effective at the stage of ARC/AIDS in a rhesus monkey infected with SIV.

The synthesis and anti-RSV (Rouse Sarcoma Virus) activity of HMCA, (+/-)-9-(2-hydroxymethyl-cyclopenthyl)-adenine, and its derivatives are described. It has been demonstrated that trans-HMCA has greater anti-RSV activity in tissue culture than cis-HMCA.