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In the midst of the battle against SARS-CoV-2

The contribution of HFSP awardees to the global effort on COVID-19 research

Since the discovery of SARS-CoV-2 and the subsequent outbreak of the Covid-19 pandemic, HFSP alumni and awardees have actively contributed to advancing knowledge about the virus. The strategy and approaches vary: sometimes in a general scientific context advancing basic understanding of the virus physiology, sometimes as advisors to the government or as inventors of novel therapeutic approaches. Below are some selected examples of successful research by HFSP awardees.

 

HFSP alumna Fernanda De Felice on the effects of Covid on the brains of Covid-19 long-haulers

Early on in the pandemic, Fernanda De Felice, a neurobiologist at the Federal University, Brazil and Queen’s University, Canada, was concerned that Covid-19 poses a risk to the brain and about the potential neurological consequences of infection (De Felice et al., 2020, Nature). However, clinicians are still in the early phases of understanding the degree of impact of the disease on the brain. Symptoms are variable and diverse. HFSP alumna Fernanda De Felice is concerned that evidence of cases from hospitalised patients may present a skewed picture as information is lacking from patients who suffered mild symptoms and no respiratory problems. According to De Felice there is uncertainty as to why Covid-19 has contrasting effects leaving some patients with symptoms for years while others experience les severe impacts on their health. She is currently examining the long-term consequences of COVID-19 infection on cognitive and brain functions in patients recovering from the infection. More knowledge is needed to understand the underlying mechanisms to establish the impact of Covid-19 on the brain.

Link to article in Nature
Link to article in Trends Neurosci.

HFSP grantee Young Seok Ju developed lab-grown mini-lungs to study infection by SARS-CoV-2

To better understand how SARS-CoV-2 infects the lungs and causes disease, Young Seok Ju of the Graduate School of Medical Science and Engineering at KAIST, in collaboration with the Wellcome-MRC Cambridge Stem Cell Institute, turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behavior of tissue and organs. Using human stem cells, his team grew self-organizing alveolar-like structures, so called mini-lungs that allowed infection and replication of the virus to be followed. By imaging-based analyses and single-cell transcriptome profiling of the infection model, his group revealed molecular interactions between the SARS-CoV-2 virus and human alveolar cells for the first three days of infection. The model further offers applications for tackling the many unanswered key questions about SARS-CoV-2, such as understanding genetic susceptibility to SARS-CoV-2, assessing relative infectivity of viral mutants, and revealing the damage processes of the virus in human alveolar cells. Most importantly, it provides the opportunity to develop and screen potential therapeutic agents against SARS-CoV-2 infection. The models are also applicable to the study of the basic biology of human alveolar cells and respiratory diseases.

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HFSP fellow Dae-Eun Jeong developed a new meta-search tool that identified SARS-CoV-2-like sequences in pangolin viromes

HFSP fellow Dae-Eun Jeong looks at nucleic acids, one of the important building blocks of life. Like any living species, viruses have their unique DNA and RNA genomic sequences and transmit the genomic information to next generations. DNA/RNA sequencing technology enables a more thorough understanding of the fundamental genomic processes in different life forms. Advanced technologies allow DNA/RNA sequencing data from a variety of living species to be produced. Even though these data are publicly available, it is not easy to search for specific DNA/RNA sequences of interest in huge datasets (individual datasets often include dozens of millions of sequence reads.) 

Jeong and his colleagues developed a low-cost, high-speed tool for enabling meta-searches through a great variety of sequencing datasets. They applied bioinformatic algorithms to facilitate sensitive and precise detection of rare transcripts from mRNA sequencing data. A meta-search tool was developed to understand how SARS-CoV-2 traversed the animal ecosphere. The team explored the distribution of SARS-CoV-2 RNA genome sequences in available ‘virome’ metagenomics datasets. The search concentrated on nucleic acid sequences that are highly similar to the SARS-CoV-2 RNA genome through the virome metagenomic datasets and unexpectedly found SARS-CoV-2-like sequences in published datasets from bat, bird, and pangolin meta-virome studies. Sequence reads that matched the SARS-CoV-2 were detected in the datasets of pangolin lung meta-viromes, raising the hypothesis that pangolins have been infected with SARS-CoV-2-like virus during the spread of the virus and in parallel or connected to potential zoonosis to humans.

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