Dev Cell. 2021 Mar 9:S1534-5807(21)00162-3. doi: 10.1016/j.devcel.2021.02.022. Online ahead of print.

ABSTRACT

Neuronal activity increases energy consumption and requires balanced production to maintain neuronal function. How activity is coupled to energy production remains incompletely understood. Here, we report that Rheb regulates mitochondrial tricarboxylic acid cycle flux of acetyl-CoA by activating pyruvate dehydrogenase (PDH) to increase ATP production. Rheb is induced by synaptic activity and lactate and dynamically trafficked to the mitochondrial matrix through its interaction with Tom20. Mitochondria-localized Rheb protein is required for activity-induced PDH activation and ATP production. Cell-type-specific gain- and loss-of-function genetic models for Rheb reveal reciprocal changes in PDH phosphorylation/activity, acetyl-CoA, and ATP that are not evident with genetic or pharmacological manipulations of mTORC1. Mechanistically, Rheb physically associates with PDH phosphatase (PDP), enhancing its activity and association with the catalytic E1α-subunit of PDH to reduce PDH phosphorylation and increase its activity. Findings identify Rheb as a nodal point that balances neuronal activity and neuroenergetics via Rheb-PDH axis.

PMID:33725483 | DOI:10.1016/j.devcel.2021.02.022

Adv Exp Med Biol. 2021;1286:49-64. doi: 10.1007/978-3-030-55035-6_3.

ABSTRACT

Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer worldwide. It metastasizes rapidly and has a poor prognosis. The first-line treatment for most patients is a combination of chemotherapy and radiation. In many subjects, using targeted treatments alongside chemoradiation has shown a better outcome in terms of progression and quality of life for patients. These targeted treatments include small biological inhibiting molecules and monoclonal antibodies. In this review, we have assessed studies focused upon the treatment of non-small cell lung cancer. Some therapies are approved, such as bevacizumab and atezolizumab, while some are still in clinical trials, such as ficlatuzumab and ipilimumab, and others have been rejected due to inadequate disease control, such as figitumumab.

PMID:33725344 | DOI:10.1007/978-3-030-55035-6_3

Metabolomics. 2021 Mar 16;17(4):35. doi: 10.1007/s11306-021-01785-4.

NO ABSTRACT

PMID:33725196 | DOI:10.1007/s11306-021-01785-4

Brief Bioinform. 2021 Mar 17:bbab061. doi: 10.1093/bib/bbab061. Online ahead of print.

ABSTRACT

The development and progression of cardiovascular disease (CVD) can mainly be attributed to the narrowing of blood vessels caused by atherosclerosis and thrombosis, which induces organ damage that will result in end-organ dysfunction characterized by events such as myocardial infarction or stroke. It is also essential to consider other contributory factors to CVD, including cardiac remodelling caused by cardiomyopathies and co-morbidities with other diseases such as chronic kidney disease. Besides, there is a growing amount of evidence linking the gut microbiota to CVD through several metabolic pathways. Hence, it is of utmost importance to decipher the underlying molecular mechanisms associated with these disease states to elucidate the development and progression of CVD. A wide array of systems biology approaches incorporating multi-omics data have emerged as an invaluable tool in establishing alterations in specific cell types and identifying modifications in signalling events that promote disease development. Here, we review recent studies that apply multi-omics approaches to further understand the underlying causes of CVD and provide possible treatment strategies by identifying novel drug targets and biomarkers. We also discuss very recent advances in gut microbiota research with an emphasis on how diet and microbial composition can impact the development of CVD. Finally, we present various biological network analyses and other independent studies that have been employed for providing mechanistic explanation and developing treatment strategies for end-stage CVD, namely myocardial infarction and stroke.

PMID:33725119 | DOI:10.1093/bib/bbab061

PLoS One. 2021 Mar 16;16(3):e0248623. doi: 10.1371/journal.pone.0248623. eCollection 2021.

ABSTRACT

Iran is a center of origin and diversity for walnuts (Juglans regia L.) with very good potential for breeding purposes. The rich germplasm available, creates an opportunity for study and selection of the diverse walnut genotypes. In this study, the population structure of 104 Persian walnut accessions was assessed using AFLP markers in combination with phenotypic variability of 17 and 18 qualitative and quantitative traits respetively. The primers E-TG/M-CAG, with high values of number of polymorphic bands, polymorphic information content, marker index and Shannon's diversity index, were the most effective in detecting genetic variation within the walnut germplasm. Multivariate analysis of variance indicated 93.98% of the genetic variability was between individuals, while 6.32% of variation was among populations. A relatively new technique, an advanced maximization strategy with a heuristic approach, was deployed to develop the core collection. Initially, three independent core collections (CC1-CC3) were created using phenotypic data and molecular markers. The three core collections (CC1-CC3) were then merged to generate a composite core collection (CC4). The mean difference percentage, variance difference percentage, variable rate of coefficient of variance percentage, coincidence rate of range percentage, Shannon's diversity index, and Nei's gene diversity were employed for comparative analysis. The CC4 with 46 accessions represented the complete range of phenotypic and genetic variability. This study is the first report describing development of a core collection in walnut using molecular marker data in combination with phenotypic values. The construction of core collection could facilitate the work for identification of genetic determinants of trait variability and aid effective utilization of diversity caused by outcrossing, in walnut breeding programs.

PMID:33725012 | DOI:10.1371/journal.pone.0248623

Elife. 2021 Mar 16;10:e57843. doi: 10.7554/eLife.57843. Online ahead of print.

ABSTRACT

Sexual activity and/or reproduction are associated with a doubling of life expectancy in the long-lived rodent genus Fukomys. To investigate the molecular mechanisms underlying this phenomenon, we analyzed 636 RNA-seq samples across 15 tissues. This analysis suggests that changes in the regulation of the hypothalamic-pituitary-adrenal stress axis play a key role regarding the extended life expectancy of reproductive vs. non-reproductive mole-rats. This is substantiated by a corpus of independent evidence. In accordance with previous studies, the up-regulation of the proteasome and so-called "anti-aging molecules", e.g. DHEA, is linked with enhanced lifespan. On the other hand, several of our results are not consistent with knowledge about aging of short-lived model organisms. For example, we found the up-regulation of the IGF1/GH axis and several other anabolic processes to be compatible with a considerable lifespan prolongation. These contradictions question the extent to which findings from short-lived species can be transferred to longer-lived ones.

PMID:33724179 | DOI:10.7554/eLife.57843

J Chem Inf Model. 2021 Mar 16. doi: 10.1021/acs.jcim.0c01160. Online ahead of print.

ABSTRACT

To reduce time and cost, virtual ligand screening (VLS) often precedes experimental ligand screening in modern drug discovery. Traditionally, high-resolution structure-based docking approaches rely on experimental structures, while ligand-based approaches need known binders to the target protein and only explore their nearby chemical space. In contrast, our structure-based FINDSITEcomb2.0 approach takes advantage of predicted, low-resolution structures and information from ligands that bind distantly related proteins whose binding sites are similar to the target protein. Using a boosted tree regression machine learning framework, we significantly improved FINDSITEcomb2.0 by integrating ligand fragment scores as encoded by molecular fingerprints with the global ligand similarity scores of FINDSITEcomb2.0. The new approach, FRAGSITE, exploits our observation that ligand fragments, e.g., rings, tend to interact with stereochemically conserved protein subpockets that also occur in evolutionarily unrelated proteins. FRAGSITE was benchmarked on the 102 protein DUD-E set, where any template protein whose sequence identify >30% to the target was excluded. Within the top 100 ranked molecules, FRAGSITE improves VLS precision and recall by 14.3 and 18.5%, respectively, relative to FINDSITEcomb2.0. Moreover, the mean top 1% enrichment factor increases from 25.2 to 30.2. On average, both outperform state-of-the-art deep learning-based methods such as AtomNet. On the more challenging unbiased set LIT-PCBA, FRAGSITE also shows better performance than ligand similarity-based and docking approaches such as two-dimensional ECFP4 and Surflex-Dock v.3066. On a subset of 23 targets from DEKOIS 2.0, FRAGSITE shows much better performance than the boosted tree regression-based, vScreenML scoring function. Experimental testing of FRAGSITE's predictions shows that it has more hits and covers a more diverse region of chemical space than FINDSITEcomb2.0. For the two proteins that were experimentally tested, DHFR, a well-studied protein that catalyzes the conversion of dihydrofolate to tetrahydrofolate, and the kinase ACVR1, FRAGSITE identified new small-molecule nanomolar binders. Interestingly, one new binder of DHFR is a kinase inhibitor predicted to bind in a new subpocket. For ACVR1, FRAGSITE identified new molecules that have diverse scaffolds and estimated nanomolar to micromolar affinities. Thus, FRAGSITE shows significant improvement over prior state-of-the-art ligand virtual screening approaches. A web server is freely available for academic users at http:/sites.gatech.edu/cssb/FRAGSITE.

PMID:33724022 | DOI:10.1021/acs.jcim.0c01160

Cell Death Differ. 2021 Mar 15. doi: 10.1038/s41418-021-00766-3. Online ahead of print.

ABSTRACT

The role of mitophagy, a process that allows the removal of damaged mitochondria from cells, remains unknown in multiple sclerosis (MS), a disease that is found associated with dysfunctional mitochondria. Here we have qualitatively and quantitatively studied the main players in PINK1-mediated mitophagy in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting MS. We found the variant c.491G>A (rs550510, p.G140E) of NDP52, one of the major mitophagy receptor genes, associated with a MS cohort. Through the characterization of this variant, we discovered that the residue 140 of human NDP52 is a crucial modulator of NDP52/LC3C binding, promoting the formation of autophagosomes in order to drive efficient mitophagy. In addition, we found that in the PBMC population, NDP52 is mainly expressed in B cells and by ensuring efficient mitophagy, it is able to limit the production of the proinflammatory cytokine TNF-α following cell stimulation. In sum, our results contribute to a better understanding of the role of NDP52 in mitophagy and underline, for the first time, a possible role of NDP52 in MS.

PMID:33723372 | DOI:10.1038/s41418-021-00766-3

Sci Rep. 2021 Mar 15;11(1):6056. doi: 10.1038/s41598-021-85595-7.

ABSTRACT

BRAF and NRAS are the most reported mutations associated to melanomagenesis. The lack of accurate diagnostic markers in response to therapeutic treatment in BRAF/NRAS-driven melanomagenesis is one of the main challenges in melanoma personalized therapy. In order to assess the diagnostic value of phosphatidylserine-specific phospholipase A1-alpha (PLA1A), a potent lysophospholipid mediating the production of lysophosphatidylserine, PLA1A mRNA and serum levels were compared in subjects with malignant melanoma (n = 18), primary melanoma (n = 13), and healthy subjects (n = 10). Additionally, the correlation between histopathological subtypes of BRAF/NRAS-mutated melanoma and PLA1A was analyzed. PLA1A expression was significantly increased during melanogenesis and positively correlated to disease severity and histopathological markers of metastatic melanoma. PLA1A mRNA and serum levels were significantly higher in patients with BRAF-mutated melanoma compared to the patients with NRAS-mutated melanoma. Notably, PLA1A can be used as a diagnostic marker for an efficient discrimination between naïve melanoma samples and advanced melanoma samples (sensitivity 91%, specificity 57%, and AUC 0.99), as well as BRAF-mutated melanoma samples (sensitivity 62%, specificity 61%, and AUC 0.75). Our findings suggest that PLA1A can be considered as a potential diagnostic marker for advanced and BRAF-mutated melanoma.

PMID:33723350 | DOI:10.1038/s41598-021-85595-7

Sci Rep. 2021 Mar 15;11(1):5913. doi: 10.1038/s41598-021-85277-4.

ABSTRACT

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. Chitin is an insoluble polysaccharide (β-(1-4)-poly-N-acetyl-D-glucosamine) and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. On the other hand, several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that-in our murine models-epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Our findings provide further insight into the underlying mechanisms of development of HDM-mediated allergic disorders.

PMID:33723298 | DOI:10.1038/s41598-021-85277-4

Sci Rep. 2021 Mar 15;11(1):5933. doi: 10.1038/s41598-021-84925-z.

ABSTRACT

Insect societies require an effective communication system to coordinate members' activities. Although eusocial species primarily use chemical communication to convey information to conspecifics, there is increasing evidence suggesting that vibroacoustic communication plays a significant role in the behavioural contexts of colony life. In this study, we sought to determine whether stridulation can convey information in ant societies. We tested three main hypotheses using the Mediterranean ant Crematogaster scutellaris: (i) stridulation informs about the emitter'caste; (ii) workers can modulate stridulation based on specific needs, such as communicating the profitability of a food resource, or (iii) behavioural contexts. We recorded the stridulations of individuals from the three castes, restrained on a substrate, and the signals emitted by foragers workers feeding on honey drops of various sizes. Signals emitted by workers and sexuates were quantitatively and qualitatively distinct as was stridulation emitted by workers on different honey drops. Comparing across the experimental setups, we demonstrated that signals emitted in different contexts (restraining vs feeding) differed in emission patterns as well as certain parameters (dominant frequency, amplitude, duration of chirp). Our findings suggest that vibrational signaling represents a flexible communication channel paralleling the well-known chemical communication system.

PMID:33723279 | DOI:10.1038/s41598-021-84925-z

Cell Death Dis. 2021 Mar 15;12(3):277. doi: 10.1038/s41419-021-03543-9.

ABSTRACT

Glioma stem cells (GSCs) contribute to therapy resistance and poor outcomes for glioma patients. A significant feature of GSCs is their ability to grow in an acidic microenvironment. However, the mechanism underlying the rewiring of their metabolism in low pH remains elusive. Here, using metabolomics and metabolic flux approaches, we cultured GSCs at pH 6.8 and pH 7.4 and found that cells cultured in low pH exhibited increased de novo purine nucleotide biosynthesis activity. The overexpression of glucose-6-phosphate dehydrogenase, encoded by G6PD or H6PD, supports the metabolic dependency of GSCs on nucleotides when cultured under acidic conditions, by enhancing the pentose phosphate pathway (PPP). The high level of reduced glutathione (GSH) under acidic conditions also causes demand for the PPP to provide NADPH. Taken together, upregulation of G6PD/H6PD in the PPP plays an important role in acidic-driven purine metabolic reprogramming and confers a predilection toward glioma progression. Our findings indicate that targeting G6PD/H6PD, which are closely related to glioma patient survival, may serve as a promising therapeutic target for improved glioblastoma therapeutics. An integrated metabolomics and metabolic flux analysis, as well as considering microenvironment and cancer stem cells, provide a precise insight into understanding cancer metabolic reprogramming.

PMID:33723244 | DOI:10.1038/s41419-021-03543-9

Proc Natl Acad Sci U S A. 2021 Mar 23;118(12):e2012800118. doi: 10.1073/pnas.2012800118.

ABSTRACT

The rise of antibiotic resistance calls for new therapeutics targeting resistance factors such as the New Delhi metallo-β-lactamase 1 (NDM-1), a bacterial enzyme that degrades β-lactam antibiotics. We present structure-guided computational methods for designing peptide macrocycles built from mixtures of l- and d-amino acids that are able to bind to and inhibit targets of therapeutic interest. Our methods explicitly consider the propensity of a peptide to favor a binding-competent conformation, which we found to predict rank order of experimentally observed IC50 values across seven designed NDM-1- inhibiting peptides. We were able to determine X-ray crystal structures of three of the designed inhibitors in complex with NDM-1, and in all three the conformation of the peptide is very close to the computationally designed model. In two of the three structures, the binding mode with NDM-1 is also very similar to the design model, while in the third, we observed an alternative binding mode likely arising from internal symmetry in the shape of the design combined with flexibility of the target. Although challenges remain in robustly predicting target backbone changes, binding mode, and the effects of mutations on binding affinity, our methods for designing ordered, binding-competent macrocycles should have broad applicability to a wide range of therapeutic targets.

PMID:33723038 | DOI:10.1073/pnas.2012800118

BMJ Open. 2021 Mar 15;11(3):e043221. doi: 10.1136/bmjopen-2020-043221.

ABSTRACT

INTRODUCTION: Research has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. The Bugs and Brains Study aims to investigate complex relationships between anxiety/depression and irritable bowel syndrome (IBS) in two ways. First, its primary component will compare the gut and oral microbiota in females with anxiety/depression and/or IBS relative to controls, and investigate underlying physiological, endocrine and immune factors, as well as associations with diet and psychosocial factors. In an ancillary component, the study will also investigate gastrointestinal and mental health symptoms in a larger sample, and explore relationships with diet, exercise, oral health, substance use, medical history, early life adversity and psychosocial factors.

METHODS AND ANALYSIS: The Bugs and Brains Study aims to recruit 160 females to the primary component: (1) 40 controls; (2) 40 participants with a depressive/anxiety disorder, but no IBS; (3) 40 participants with IBS, but no depressive/anxiety disorder and (4) 40 participants with both depressive/anxiety disorder and IBS. Participation is completed within 1 month, and involves comprehensive questionnaires, anthropometrics, a diagnostic clinical interview, collection of two saliva samples, and stool, urine and hair samples. This study aims to use a systems biology approach to characterise oral and gut microbial composition and function using 16S rRNA gene sequencing and nuclear MR spectroscopy. As part of the ancillary component, it will collect questionnaire data from 1000 participants aged 18-40 years, capturing mental health, gastrointestinal health, oral health, diet and psychosocial factors.

ETHICS AND DISSEMINATION: Approval was granted by the University of Melbourne Human Research Ethics Committee (#1749221). All participants voluntarily provided informed consent. Results will be published in peer-reviewed journals and presented at scientific conferences.

PMID:33722869 | DOI:10.1136/bmjopen-2020-043221

J Sport Health Sci. 2021 Mar 12:S2095-2546(21)00027-2. doi: 10.1016/j.jshs.2021.03.002. Online ahead of print.

NO ABSTRACT

PMID:33722759 | DOI:10.1016/j.jshs.2021.03.002

Methods. 2021 Mar 12:S1046-2023(21)00072-4. doi: 10.1016/j.ymeth.2021.03.006. Online ahead of print.

ABSTRACT

Viral load monitoring in human immunodeficiency virus type 1 (HIV-1) infection is often performed using reverse transcription quantitative PCR (RT-qPCR) to observe response to treatment and identify the development of resistance. Traceability is achieved using a calibration hierarchy traceable to the International Unit (IU). IU values are determined using consensus agreement derived from estimations by different laboratories. Such a consensus approach is necessary due to the fact that there are currently no reference measurement procedures available that can independently assign a reference value to viral reference materials for molecular in vitro diagnostic tests. Digital PCR (dPCR) is a technique that has the potential to be used for this purpose. In this paper, we investigate the ability of reverse transcriptase dPCR (RT-dPCR) to quantify HIV-1 genomic RNA without calibration. Criteria investigated included the performance of HIV-1 RNA extraction steps, choice of reverse transcription approach and selection of target gene with assays performed in both single and duplex format. We developed a protocol which was subsequently applied by two independent laboratories as part of an external quality assurance (EQA) scheme for HIV-1 genome detection. Our findings suggest that RT-dPCR could be used as reference measurement procedure to aid the value assignment of HIV-1 reference materials to support routine calibration of HIV-1 viral load testing by RT-qPCR.

PMID:33722693 | DOI:10.1016/j.ymeth.2021.03.006

Mol Metab. 2021 Mar 12:101210. doi: 10.1016/j.molmet.2021.101210. Online ahead of print.

ABSTRACT

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a silent pandemic associated with obesity and the Metabolic Syndrome, linked to increased cardiovascular- and cirrhosis-related morbidity and mortality. A complete understanding of the adaptive compensatory metabolic programs that modulate non-alcoholic steatohepatitis (NASH) progression is missing.

METHODS AND RESULTS: Transcriptomics analysis of liver biopsies in patients with NASH revealed that NASH progression is associated with rewiring of metabolic pathways, including upregulation of the de novo lipid/cholesterol synthesis and fatty acid remodelling. The modulation of these metabolic programs was achieved through the activation of Sterol Regulatory Element-Binding Proteins (SREBPs) transcriptional networks; however, it is still debated whether, in the context of NASH, activation of SREBPs acts as a pathogenic driver of lipotoxicity, or promotes the biosynthesis of protective lipids that buffer excessive lipid accumulation, preventing inflammation and fibrosis. To elucidate the pathophysiological role of SCAP/SREBP's in NASH and wound-healing response, we used an Insig1 deficient hyper-efficient SREBP activator murine model. Despite enhanced lipid and cholesterol biosynthesis the Insig1 KO mice had similar systemic metabolism and insulin sensitivity to Het/WT littermates. Moreover, the activation of SREBPs resulted in the remodelling of the lipidome, decreased hepatocellular damage, and improved wound-healing responses.

CONCLUSION: Our study provides actionable knowledge about the pathways and mechanisms involved in NAFLD pathogenesis, which may prove useful for the development of new therapeutic strategies. Moreover, our results suggest that the SCAP/SREBP/INSIG1 trio governs transcriptional programs aimed at protecting the liver from lipotoxic insults in NASH.

PMID:33722690 | DOI:10.1016/j.molmet.2021.101210

Metab Eng. 2021 Mar 12:S1096-7176(21)00044-6. doi: 10.1016/j.ymben.2021.03.008. Online ahead of print.

ABSTRACT

The economic viability of current bio-production systems is often limited by its low productivity due to slow cell growth and low substrate uptake rate. The fastest-growing bacterium Vibrio natriegens is a highly promising next-generation workhorse of the biotechnology industry which can utilize various industrially relevant carbon sources with high substrate uptake rates. Here, we demonstrate the first systematic engineering example of V. natriegens for the heterologous production of 1,3-propanediol (1,3-PDO) from glycerol. Systems metabolic engineering strategies have been applied in this study to develop a superior 1,3-PDO producer, including: (1) heterologous pathway construction and optimization; (2) engineering cellular transcriptional regulators and global transcriptomic analysis; (3) enhancing intracellular reducing power by cofactor engineering; (4) reducing the accumulation of toxic intermediate by pathway engineering; (5) systematic engineering of glycerol oxidation pathway to eliminate byproduct formation. A final engineered strain can efficiently produce 1,3-PDO with a titer of 56.2 g/L, a yield of 0.61 mol/mol, and an average productivity of 2.36 g/L/h. The strategies described in this study would be useful for engineering V. natriegens as a potential chassis for the production of other useful chemicals and biofuels.

PMID:33722653 | DOI:10.1016/j.ymben.2021.03.008

Antiviral Res. 2021 Mar 12:105062. doi: 10.1016/j.antiviral.2021.105062. Online ahead of print.

ABSTRACT

We recently reported that some clinically approved antifungal drugs are potent inhibitors of human cytomegalovirus (HCMV). Here, we report the broad-spectrum activity against HCMV of isavuconazole (ICZ), a new extended-spectrum triazolic antifungal drug. ICZ inhibited the replication of clinical isolates of HCMV as well as strains resistant to the currently available DNA polymerase inhibitors. The antiviral activity of ICZ against HCMV could be linked to the inhibition of human cytochrome P450 51 (hCYP51), an enzyme whose activity we previously demonstrated to be required for productive HCMV infection. Moreover, time-of-addition studies indicated that ICZ might have additional inhibitory effects during the first phase of HCMV replication. Importantly, ICZ showed synergistic antiviral activity in vitro when administered in combination with different approved anti-HCMV drugs at clinically relevant doses. Together, these results pave the way to possible future clinical studies aimed at evaluating the repurposing potential of ICZ in the treatment of HCMV-associated diseases.

PMID:33722615 | DOI:10.1016/j.antiviral.2021.105062

J Genet Genomics. 2021 Feb 10:S1673-8527(21)00017-5. doi: 10.1016/j.jgg.2020.12.001. Online ahead of print.

NO ABSTRACT

PMID:33722521 | DOI:10.1016/j.jgg.2020.12.001