AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

DS_DISC767844 – Supplemental material for A Fragment Library Screening Approach to Identify Selective Inhibitors against an Essential Fungal Enzyme

<p>Supplemental material, DS_DISC767844 for A Fragment Library Screening Approach to Identify Selective Inhibitors against an Essential Fungal Enzyme by Gopal P. Dahal and Ronald E. Viola in SLAS Discovery</p

Agricultural innovation and adaptation to climate change: empirical evidence from diverse agro-ecologies in South Asia

While impacts of climate change on agricultural systems have been widely researched, there is still limited understanding of what agricultural innovations have evolved over time in response to both climatic and non-climatic drivers. Although there has been some progress in formulating national adaptation policies and strategic planning in different countries of South Asia, research to identify local-level adaptive strategies and practices is still limited. Through eight case studies and a survey of 300 households in 15 locations in India, Nepal and Bangladesh, this paper generates empirical evidence on emerging agricultural innovations in contrasting socio-economic, geographical and agro-ecological contexts. The study demonstrates that several farm practices (innovations) have emerged in response to multiple drivers over time, with various forms of institutional and policy support, including incentives to reduce risks in the adoption of innovative practice. It further shows that there is still limited attempt to systematically mainstream adaptation innovations into local, regional and national government structures, policies and planning processes. The paper shows that the process of farm-level adaptation through innovation adoption forms an important avenue for agricultural adaptation in South Asia. A key implication of this finding is that there is a need for stronger collaborations between research institutions, extension systems, civil society and the private sector actors to enhance emerging adaptive innovations at the farm level

Village-integrated eye workers for prevention of corneal ulcers in Nepal (VIEW study): a cluster-randomised controlled trial

BackgroundCorneal ulcers are a common cause of blindness in low-income and middle-income countries, usually resulting from traumatic corneal abrasions during agricultural work. Antimicrobial prophylaxis of corneal abrasions can help prevent corneal ulcers, but delays in the initiation of therapy are frequent. We aimed to assess whether a community-based programme for corneal ulcer prevention would reduce the incidence of corneal ulceration.MethodsA cluster-randomised trial was performed in village development committees (VDCs) in Nepal. VDCs in the catchment area of Bharatpur Eye Hospital, Nepal with less than 15 000 people were eligible for inclusion. We randomly assigned (1:1) VDCs to either an intervention group or a control group. In the intervention VDCs, existing female community health volunteers (FCHVs) were trained to diagnose corneal abrasions and provide a 3-day course of ophthalmic antimicrobials to their patients. In the control VDCs, FCHVs did not provide this intervention. Participants were not masked given the nature of the intervention. Both groups were followed up for 3 years for photographic evidence of corneal ulceration. The primary outcome was the incidence of corneal ulceration, determined by masked assessment of corneal photographs. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01969786.FindingsWe assessed 112 VDCs, of which 24 were enrolled. The study was performed between Feb 4, 2014, and Oct 20, 2017. 12 VDCs were randomly assigned to the intervention group and 12 to the control group. 252 539 individuals were included in the study (130 579 in the intervention group and 121 960 in the control group). FCHVs diagnosed and provided antimicrobials for 4777 corneal abrasions. The census identified 289 corneal ulcers among 246 893 person-years in the intervention group (incidence 1·21 cases [95% CI 0·85-1·74] per 1000 person-years) and 262 corneal ulcers among 239 170 person-years in the control group (incidence 1·18 cases [0·82-1·70] per 1000 person-years; incidence rate ratio 1·03 [95% CI 0·63-1·67]; p=0·93). Medication allergy was self-reported in 0·2% of participants.InterpretationWe did not detect a reduction in the incidence of corneal ulceration during the first 3 years of a community-based corneal ulcer prevention programme. Further study might be warranted in more rural areas where basic eye care facilities are not available.FundingNational Eye Institute