At a crucial time with rapid spread of Omicron SARS-CoV-2 virus variant globally, the United States Food and Drug Administration has issued an emergency use authorization for two oral antivirals molnupiravir (>18 years) and nirmatrelvir-ritonavir (Paxlovid) (≥12 years; >40kg ) for the outpatient treatment of mild to moderate COVID–19 patients who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is an HIV-1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within five days of symptoms onset and given for five days duration. This article will review the two oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.

BackgroundSoil-borne fungi of the Fusarium oxysporum species complex cause devastating wilt disease on many crops including legumes that supply human dietary protein needs across many parts of the globe. We present and compare draft genome assemblies for three legume-infecting formae speciales (ff. spp.): F. oxysporum f. sp. ciceris (Foc-38-1) and f. sp. pisi (Fop-37622), significant pathogens of chickpea and pea respectively, the world’s second and third most important grain legumes, and lastly f. sp. medicaginis (Fom-5190a) for which we developed a model legume pathosystem utilising Medicago truncatula.ResultsFocusing on the identification of pathogenicity gene content, we leveraged the reference genomes of Fusarium pathogens F. oxysporum f. sp. lycopersici (tomato-infecting) and F. solani (pea-infecting) and their well-characterised core and dispensable chromosomes to predict genomic organisation in the newly sequenced legume-infecting isolates. Dispensable chromosomes are not essential for growth and in Fusarium species are known to be enriched in host-specificity and pathogenicity-associated genes. Comparative genomics of the publicly available Fusarium species revealed differential patterns of sequence conservation across F. oxysporum formae speciales, with legume-pathogenic formae speciales not exhibiting greater sequence conservation between them relative to non-legume-infecting formae speciales, possibly indicating the lack of a common ancestral source for legume pathogenicity. Combining predicted dispensable gene content with in planta expression in the model legume-infecting isolate, we identified small conserved regions and candidate effectors, four of which shared greatest similarity to proteins from another legume-infecting ff. spp.ConclusionsWe demonstrate that distinction of core and potential dispensable genomic regions of novel F. oxysporum genomes is an effective tool to facilitate effector discovery and the identification of gene content possibly linked to host specificity. While the legume-infecting isolates didn’t share large genomic regions of pathogenicity-related content, smaller regions and candidate effector proteins were highly conserved, suggesting that they may play specific roles in inducing disease on legume hosts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2486-8) contains supplementary material, which is available to authorized users.

Analyses of frequency profiles of markers on disease or drug-response related genes in diverse populations are important for the dissection of common diseases. We report the results of analyses of data on 405 SNPs from 75 such genes and a 5.2 Mb chromosome, 22 genomic region in 1871 individuals from diverse 55 endogamous Indian populations. These include 32 large (>10 million individuals) and 23 isolated populations, representing a large fraction of the people of India. We observe high levels of genetic divergence between groups of populations that cluster largely on the basis of ethnicity and language. Indian populations not only overlap with the diversity of HapMap populations, but also contain population groups that are genetically distinct. These data and results are useful for addressing stratification and study design issues in complex traits especially for heterogeneous populations.

The results of this hypothetical acceptability study indicate that these low-income women in Delhi are: willing to try vaginal rings; unconcerned about wearing them during sex; very interested in protection from infections and unintended pregnancy; indifferent about colour of new rings; emphatic about being told that rings may change colour from menstrual blood staining; comfortable with thinner rings; willing to try thicker rings once familiar with thinner rings; in favour of starting with 1-month rings and then transitioning to longer-term rings; and in favour of first accessing rings at a facility and then managing resupply independently.

Summary Ascochyta blight ( AB ) is one of the major biotic stresses known to limit the chickpea production worldwide. To dissect the complex mechanisms of AB resistance in chickpea, three approaches, namely, transcriptome, small RNA and degradome sequencing were used. The transcriptome sequencing of 20 samples including two resistant genotypes, two susceptible genotypes and one introgression line under control and stress conditions at two time points (3rd and 7th day post inoculation) identified a total of 6767 differentially expressed genes ( DEG s). These DEG s were mainly related to pathogenesis‐related proteins, disease resistance genes like NBS ‐ LRR , cell wall biosynthesis and various secondary metabolite synthesis genes. The small RNA sequencing of the samples resulted in the identification of 651 mi RNA s which included 478 known and 173 novel mi RNA s. A total of 297 mi RNA s were differentially expressed between different genotypes, conditions and time points. Using degradome sequencing and in silico approaches, 2131 targets were predicted for 629 mi RNA s. The combined analysis of both small RNA and transcriptome datasets identified 12 mi RNA ‐ mRNA interaction pairs that exhibited contrasting expression in resistant and susceptible genotypes and also, a subset of genes that might be post‐transcriptionally silenced during AB infection. The comprehensive integrated analysis in the study provides better insights into the transcriptome dynamics and regulatory network components associated with AB stress in chickpea and, also offers candidate genes for chickpea improvement.

In our study, INPP4A was identified as a novel asthma candidate gene, whereby the +110832A/G (Thr/Ala) variant affected its stability and was significantly associated with asthma.

Methyl nonanoate was synthesized in a batch reactor by esterification of nonanoic acid with methanol catalyzed by the cation exchange resins, Dowex 50Wx2, Amberlyst 35, and Amberlyst 15. The effect of various parameters such as speed of agitation, catalyst loading, molar ratio, and reaction temperature on degree of conversion has been reported. The conversion of nonanoic acid to methyl nonanoate was found to increase with an increase in temperature in the range of 303.15−333.15 K and the increase was appreciable with an excess use of methanol in the reaction mixture. Nonideality of the liquid phase was taken into account by using activities instead of concentration. The activity coefficients were calculated using the UNIFAC group contribution method. The possible mechanism of reaction was mathematically treated using theories of the Eley−Rideal model based on inhibition by water and methanol on the Amberlyst 15. The reaction rate constants and the adsorption coefficients for methanol and water were determined from the experimental data established at three different temperatures for the effect of initial concentration of acid and alcohol. The kinetics reported in this study was obtained under conditions free of both external and internal mass transfer resistance. Activation energy and pre-exponential factor of the reaction were found to be 47.6 kJ mol −1 and 3.2 × 10 4 L 2 g −1 mol −1 h −1 , respectively.

A comprehensive kinetic investigation of the esterification of nonanoic acid with 1-propanol in the liquid phase was carried out using Amberlyst 15. Kinetic experiments were conducted using a batch reactor system at a stirrer speed of 500 rpm over the temperature range 323.15 −363.15 K. The catalyst loading was varied from 4% (w/v) to 8% (w/v), and acid to alcohol molar ratios of 1:1, 1:5, 1:10, and 1:15 were used. It was found that both external and internal diffusion limitations did not affect the overall reaction rate. The conversion of nonanoic acid increased with increasing temperature and catalyst loading. The Eley−Rideal (E−R) model was tested to correlate the kinetic data, and the activity coefficients were estimated using the UNIFAC model to account for the nonideal thermodynamic behavior of reactants and products. The model predicted the kinetic behavior of the studied system reasonably well. Water was found to be more strongly adsorbed than other species present in the system. The activation energy, preexponential factor, and standard enthalpy for the esterification was estimated to be 55.4 kJ/ mol, 2.3 × 10 5 L 2 g −1 mol −1 h −1 , and −218.08 J•mol −1 , respectively, by this model. The influence of alcohol carbon chain length was studied, and their effects on reaction kinetics were compared. It was observed that activation energy increases with increases in chain lengths of alcohols.