Enzyme-catalyzed reactions have begun to transform pharmaceutical manufacturing, offering levels of selectivity and tunability that can dramatically improve chemical synthesis. Combining enzymatic reactions into multistep biocatalytic cascades brings additional benefits. Cascades avoid the waste generated by purification of intermediates. They also allow reactions to be linked together to overcome an unfavorable equilibrium or avoid the accumulation of unstable or inhibitory intermediates. We report an in vitro biocatalytic cascade synthesis of the investigational HIV treatment islatravir. Five enzymes were engineered through directed evolution to act on non-natural substrates. These were combined with four auxiliary enzymes to construct islatravir from simple building blocks in a three-step biocatalytic cascade. The overall synthesis requires fewer than half the number of steps of the previously reported routes.

A comprehensive control strategy based on interventions to reduce the rate of transmission of S. japonicum infection from cattle and humans to snails was highly effective. These interventions have been adopted as the national strategy to control schistosomiasis in China.

Several mechanisms driving SARS-CoV-2 transmission remain unclear. Based on individual records of 1178 potential SARS-CoV-2 infectors and their 15,648 contacts in Hunan, China, we estimated key transmission parameters. The mean generation time was estimated to be 5.7 (median: 5.5, IQR: 4.5, 6.8) days, with infectiousness peaking 1.8 days before symptom onset, with 95% of transmission events occurring between 8.8 days before and 9.5 days after symptom onset. Most transmission events occurred during the pre-symptomatic phase (59.2%). SARS-CoV-2 susceptibility to infection increases with age, while transmissibility is not significantly different between age groups and between symptomatic and asymptomatic individuals. Contacts in households and exposure to first-generation cases are associated with higher odds of transmission. Our findings support the hypothesis that children can effectively transmit SARS-CoV-2 and highlight how pre-symptomatic and asymptomatic transmission can hinder control efforts.

Although the number of human infections decreased, human prevalence increased from 4.9% in 1995 to 5.1% in 2004.