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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

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NSP5 (4)

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    Successful Treatment of Convalescent Plasma Therapy in Three Patients With Severe SARS-CoV-2 Infection MESHD SARS-CoV-2 Infection MESHD in Fuzhou, China

    Authors: Di Wu; Xiaolin Zhu; Songjing Shi; Fenghui Lin; Baosong Xie; Guoxiang Lai; Lizhou Chen

    doi:10.21203/rs.3.rs-196885/v1 Date: 2021-02-01 Source: ResearchSquare

    Background Up to now, there is no specific treatment for coronavirus disease 2019 MESHD ( COVID-19 MESHD) yet except for general supportive care. Hence, it will be critical to find a new strategy for COVID-19 MESHD. The study is to explore whether convalescent plasma transfusion may be beneficial in the treatment of severe patients with COVID-19 MESHD.Methods This is a retrospective analysis of three severe patients with laboratory-confirmed COVID-19 MESHD and admitted in Fuzhou pulmonary hospital of Fujian province from February 18th, to May 15th,who met the following criteria: (1) within 3 weeks of symptom onset;laboratory confirmed cases or who had viremia MESHD conformed by clinical experts;(2)Severe patients with rapidly progress or the early stage of critically ill MESHD patients or who required plasma therapy were comprehensively evaluated by clinical experts. The data of clinical manifestations and the progresses of disease monitored by blood-gas analysis, biochemical tests, routine examine, radiological exam were abstracted and then analysis the changes before and after convalescent plasma transfusion. Results All three patients (one male and two females; age range, 57-65years) were treated with convalescent plasma during the study. Two patients had underlying chronic diseases MESHD, including diabetes MESHD and hypertension MESHD. The most common symptoms were fever MESHD (three cases, 3/3) and cough (two cases, 2/3). All patients were treated with a combination of two antiviral drugs (lopinaviritonavir or arbidol combined with IFN- HGNCɑ), whereas none of the patients were given glucocorticoids. Following plasma transfusion, the symptoms of the whole group improved to some degree, mainly manifested as reducing in coughing and body temperature normalized. Several parameters tended to improve as compared to pre-transfusion, including increased lymphocyte counts (0.97 × 109/L vs. 1.08 × 109/L) and decreased IL-6 HGNC (41.34 pg/ml vs. 13.83 pg/ml). The density of bilateral infiltration on CT imaging showed varying degrees of absorption within 7days. Throat swab nucleic acid test of most patients became negative for the novel coronavirus within 3 days after the transfusion. No adverse effects and severe complications were observed. Conclusions In this preliminary uncontrolled case series of 3severe patients with COVID-19 MESHD, convalescent plasma could be as a promising therapy for COVID-19 MESHD without corticosteroids and no serious adverse reactions associated with the transfusion of convalescent plasma were observed, which would improve the clinical outcomes following by improvement in their clinical status. Using the convalescent plasma at the early stage(less than 10 days) of disease could be more effective. Anticoagulation is necessary for severe patients with COVID-19 MESHD given the state of hypercoagulability MESHD. However, given the small sample size and limited study design, naturally these results should be taken with a grain of salt until replicated by other further investigation in larger well-controlled trials.

    The Significance of KL-6 HGNC as Prognosis Monitoring Biomarker in Patients With Severe COVID-19 MESHD From Stabilized Stage Toward Convalescence

    Authors: Long He; Liu Lu; Ming Zong; Huang Zhou; Lan Wang; Nian Zhen Chen; Jia Yi Yuan; Er Peng Jiang; Liang Zheng; Qiang Li; Lie Ying Fan; Zhong Min Liu

    doi:10.21203/rs.3.rs-191056/v1 Date: 2021-01-30 Source: ResearchSquare

    Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury MESHD in severe COVID-19 MESHD patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 MESHD (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC, TNF-α HGNC, IFN-α, IFN-γ HGNC), type II alveolar epithelium injury MESHD indicators ( Surfactant protein A HGNC ( SP-A HGNC), Krebs von den Lungen-6 HGNC von MESHD den Lungen-6 ( KL-6 HGNC)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-12p70, TNF-α HGNC) had bounced back to normal (p>0.05). Some cytokines ( IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-17A HGNC, IFN-α, IFN-γ HGNC) and type II alveolar epithelium injury MESHD indicators ( SP-A HGNC and KL-6 HGNC) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC IFN-γ HGNC, IFN-α, SP-A HGNC and KL-6 HGNC were downward trend (p<0.05), only KL-6 HGNC level (p<0.05) could simultaneously reflect the lung injury MESHD volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 HGNC could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 MESHD from stabilized stage toward convalescence.

    Identification of Serum Prognostic Biomarkers of Severe  COVID-19 MESHD by Quantitative Proteomic Approach

    Authors: Yayoi Kimura; Yusuke Nakai; Jihey Shin; Miyui Hara; Yuriko Takeda; Sousuke Kubo; Sundararaj S Jeremiah; Yoko Ino; Tomoko Akiyama; Kayano Moriyama; Kazuya Sakai; Ryo Saji; Mototsugu Nishii; Hideya Kitamura; Kota Murohashi; Kouji Yamamoto; Takeshi Kaneko; Ichiro Takeuchi; Eri Hagiwara; Takashi Ogura; Hideki Hasegawa; Tomohiko Tamura; Takeharu Yamanaka; Akihide Ryo

    doi:10.21203/rs.3.rs-156575/v1 Date: 2021-01-27 Source: ResearchSquare

    The COVID-19 pandemic MESHD is an unprecedented threat to humanity provoking global health concerns. Since the etio-pathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. An accurate prediction of the disease progression can aid in appropriate patient categorization to determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins closely associated with the prognosis of COVID-19 MESHD. We observed 27 proteins to be differentially expressed between the cohorts of severely ill COVID-19 MESHD patients with adverse and favorable prognosis. Ingenuity pathway analysis revealed that 15 out of the 27 proteins might be regulated by cytokine signalling relevant to interleukin (IL)-1b HGNC, IL-6 HGNC and tumor necrosis factor HGNC tumor necrosis factor MESHD ( TNF HGNC), and their differential expression was possibly implicated in the systemic inflammatory response and cardiovascular disorders MESHD. We further evaluated the practical prognosticators for the clinical prognosis of severe COVID-19 MESHD patients. Subsequent ELISA analyses further uncovered that CHI3L1 HGNC and IGFALS HGNC could be potent prognostic markers with a high sensitivity. Our findings can help in formulating a diagnostic approach for accurately discriminating severe COVID-19 MESHD patients and provide appropriate treatment based on their predicted prognosis.

    ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 MESHD Patients

    Authors: Eleni Karakike; George N Dalekos; Ioannis Koutsodimitropoulos; Maria Saridaki; Chryssa Pourzitaki; Georgios Papathanakos; Antigone Kotsaki; Stamatios Chalvatzis; Vasiliki Dimakopoulou; Nikolaos Vechlidis; Elisabeth Paramythiotou; Christina Avgoustou; Aikaterini Ioakeimidou; Elli Kouriannidi; Apostolos Komnos; Evangelia Neou; Nikoletta Rovina; Eleni Stefanatou; Haralampos Milionis; George Nikolaidis; Antonia Koutsoukou; Georgia Damoraki; George Dimopoulos; Vassileios Zoumpos; Jesper Eugen-Olsen; Karolina Akinosoglou; Nikolaos K Gatselis; Vasilios Koulouras; Eleni Gkeka; Nikolaos Markou; Mihai G Netea; Evangelos J Giamarellos-Bourboulis

    doi:10.1101/2021.01.20.21250182 Date: 2021-01-26 Source: medRxiv

    ABSTRACT Rationale Macrophage activation syndrome MESHD ( MAS MESHD) and complex immune dysregulation MESHD ( CID MESHD) often underlie acute respiratory distress MESHD (ARDS) in COVID-19 MESHD. Objective To investigate the outcome of personalized immunotherapy in critical COVID-19 MESHD. Methods In this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score [≥]2 or ARDS by SARS-CoV-2 were screened for MAS MESHD (ferritin more than 4420 ng/ml) and CID MESHD (ferritin [≤]4420 ng/ml and low expression of HLA-DR on CD14 HGNC-monocytes). Patients with MAS MESHD and CID MESHD with increased aminotransferases were assigned to intravenous anakinra; those with CID MESHD and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints. Measurements and Main Results The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6 HGNC, soluble urokinase plasminogen activator receptor HGNC (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6 HGNC. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment. Conclusions Biomarkers may guide favourable anakinra responses in critically ill MESHD patients with COVID-19 MESHD. Trial Registration: ClinicalTrials.gov, NCT04339712 Key-words: anakinra; tocilizumab; acute respiratory distress syndrome MESHD; COVID-19 MESHD; interleukin-6 HGNC; ferritin; HLA-DR; macrophage activation; monocytes Abstract Word count: 250

    Patients with Asthma and Chronic Obstructive Pulmonary Disease MESHD ( COPD MESHD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19 MESHD

    Authors: Nathalie Acevedo; Jose Miguel Escamilla-Gil; Hector Espinoza; Ronald Regino; Jonathan Ramirez; Lucila Florez De Arco; Rodolfo Dennis; Carlos Torres-Duque; Luis Caraballo

    doi:10.1101/2021.01.23.21250370 Date: 2021-01-26 Source: medRxiv

    BackgroundChronic obstructive pulmonary disease MESHD ( COPD MESHD) is associated with increased risk of severe COVID-19 MESHD, but the mechanisms are unclear. Besides, patients with severe COVID-19 MESHD have been reported to have increased levels of several immune mediators. ObjectiveTo perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma MESHD and COPD and to evaluate their relationship with biomarkers of severe COVID-19 MESHD. MethodsNinety-two proteins were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic MESHD. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection MESHD reported in the " COVID-19 MESHD Drug and Gene Set Library" and with known protein biomarkers of severe COVID-19 MESHD. ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 HGNC while COPD patients have a broader systemic inflammatory dysregulation driven by HGF HGNC, OPG HGNC, and several chemokines ( CXCL9 HGNC, CXCL10 HGNC, CXCL11 HGNC, CX3CL1 HGNC, CXCL1 HGNC, MCP-3 HGNC, MCP-4 HGNC, CCL3 HGNC, CCL4 HGNC and CCL11 HGNC). These proteins are involved in chemokine signaling pathways related with response to viral infections MESHD and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 MESHD Related Gene Sets database. An increase of HPG, CXCL9 HGNC, CXCL10 HGNC, IL-6 HGNC, MCP-3 HGNC, TNF HGNC and EN-RAGE HGNC has also been found in patients with severe COVID-19 MESHD. ConclusionsCOPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19 MESHD. Our study suggests that COPD patients have a systemic dysregulation MESHD in chemokine networks (including HGF HGNC and CXCL9 HGNC) that could make them more susceptible to severe COVID-19 MESHD. Our study also suggest that IL-6 HGNC levels are increased in some asthmatics and this may influence their immune response to COVID-19 MESHD.

    Home-based management of COVID-19 MESHD by identification of low-risk features

    Authors: Fernando Cabanillas; Javier Morales; Jorge Bertran-Pasarell; Ricardo Fernandez; Jose G. Conde; Yaimara Hernandez-Silva; Idalia Liboy

    doi:10.1101/2021.01.25.21249684 Date: 2021-01-26 Source: medRxiv

    Abstract Background: Covid-19 MESHD is a triphasic disorder characterized by a viral phase lasting 7-10 days from onset of symptoms. In approximately 20% it is followed by a second stage heralded by elevation of pro-inflammatory markers such as ferritin, IL-6 HGNC, CRP, LDH and D-dimers. We hypothesized that those with few abnormalities would have a low risk for progression to respiratory insufficiency MESHD and hence could be monitored at home without treatment. Methods: Inclusion criteria included Covid infection, age >21, Oxygen saturation >90%. To be observed without treatment, patients could have no more than 1 of the following: CRP > 10 mg/dL, high LDH, ferritin > 500 ng/ml, D-dimer > 1 mg/L, IL-6 HGNC > 10 pg/ml, absolute lymphocyte count <1,000, Oxygen saturation <94%, or CT chest evidence of pneumonia MESHD. Primary endpoint was progression to respiratory failure MESHD and secondary endpoints was 28-day survival. Results: Of 208 entered, 132 were low-risk and hence were monitored without therapy. None progressed to respiratory failure MESHD or died. Conclusions: We have shown that our approach can identify cases who can safely be observed without treatment, thus avoiding expensive, potentially toxic therapies, and circumventing unnecessary, costly hospitalizations. These results support our hypothesis that applying our criteria, 64% of Covid-19 MESHD cases can be monitored as outpatients without therapy.

    In vitro infection of human lung tissue with SARS-CoV-2: Heterogeneity in host defense and therapeutic response

    Authors: Matthew A Schaller; Yamini Sharma; Zadia Dupee; Duy T Nguyen; Juan M Uruena; Ryan A Smolcheck; Julia C. Loeb; Tiago N Machuca; John A Lednicky; David Odde; Robert F Campbell; W. Gregory Sawyer; Borna Mehrad; Reem Temsah; Shelaweeh Alanazi; Fahad Alzamil; Ali Alsomaily; Jafar A. Al-Tawfiq; Amr Jamal; Ali M Somily

    doi:10.1101/2021.01.20.427541 Date: 2021-01-21 Source: bioRxiv

    Cell lines are the mainstay in understanding the biology of COVID-19 MESHD infection, but do not recapitulate many of the complexities of human infection. The use of human lung tissue is one solution for the study of such novel respiratory pathogens. We hypothesized that a cryopreserved bank of human lung tissue allows for the in vitro study of the inter-individual heterogeneity of host response to SARS-CoV-2 infection MESHD, thus providing a bridge between studies with cell lines and studies in animal models. We generated a cryobank of tissues from 16 donors, most of whom had risk factors for severe illness from COVID-19 MESHD. Cryopreserved tissues preserved 90% of cell viability and contained heterogeneous populations of metabolically active epithelial, endothelial, and immune cell subsets of the human lung. Samples were readily infectible with HCoV-OC43 and SARS-CoV-2 coronavirus strains, and demonstrated comparable susceptibility to infection. In contrast, we observed a marked donor-dependent heterogeneity in the expression of IL-6 HGNC, CXCL8 HGNC and IFN{beta} in response to SARS-CoV-2 infection MESHD. Treatment of tissues with dexamethasone and the experimental drug, N-hydroxycytidine, suppressed viral growth in all samples, whereas chloroquine and remdesivir had no detectable effect. Metformin and sirolimus, molecules with predicted antiviral activity, suppressed viral replication in tissues from a subset of donors. In summary, we developed a novel system for the in vitro study of human SARS-CoV-2 infection MESHD using primary human lung tissue from a library of donor tissues. This model may be useful for drug screening and for understanding basic mechanisms of COVID-19 MESHD pathogenesis.

    Impact of Pulse D Therapy on The Inflammatory Markers in Patients With COVID-19 MESHD.

    Authors: Dr. Maheshwar Lakkireddy; Dr. Srikanth Goud Gadiga; Dr. R.D. Malathi; Dr. Madhu Latha Karra; Dr. I S S V Prasad Murthy Raju; Dr Ragini; Dr. Sangeetha Chinapaka; Dr. Sai Baba KSS; Dr. Manohar Kandakatla

    doi:10.21203/rs.3.rs-152494/v1 Date: 2021-01-21 Source: ResearchSquare

    Introduction: COVID 19 is known to cause immune dysregulation MESHD and vitamin D is a known immunomodulator. This study aims to objectively investigate the impact of Pulse D therapy in reducing the inflammatory markers of COVID-19 MESHD. Materials/ Methods: Consented COVID-19 MESHD patients with hypovitaminosis D were evaluated for inflammatory markers (N/L ratio, CRP HGNC, LDH, IL6 HGNC, Ferritin) along with vitamin D on 0th day and 9th / 11th day as per their respective BMI category. Subjects were randomised into VD and NVD groups. VD group received Pulse D therapy (targeted daily supplementation of 60,000 IUs of vitamin D for 8 or 10 days depending upon their BMI) in addition to the standard treatment. NVD group received standard treatment alone. Differences in the variables between the two groups were analysed for statistical significance. Results: Eighty seven out of one hundred and thirty subjects have completed the study (VD:44, NVD:43). Vitamin D level has increased from 15.65 ± 5.54 ng/ml to 88.96 ± 31.55 ng/ml after Pulse D therapy in VD group and highly significant (p<0.01) reduction of all the measured inflammatory markers was noted. Reduction of markers in NVD group was insignificant (p>0.05) . The difference in the reduction of markers between the groups (NVD vs VD) was highly significant (p<0.01). Conclusions: Therapeutic improvement in vitamin D to 80-100 ng/ml has significantly reduced the inflammatory markers associated with COVID-19 MESHD without any side effects. Hence, adjunctive Pulse D therapy can be added safely to the existing treatment protocols of COVID-19 MESHD for improved outcomes. 

    Clinical utility of Corona Virus Disease MESHD-19 serum IgG, IgM, and neutralizing antibodies and inflammatory markers

    Authors: Ernst J Schaefer; Florence Comite; Latha Dulipsingh; Maxine Lang; Jessica Jimison; Martin M Grajower; Nathan E Lebowitz; Andrew S Geller; Margaret R Diffenderfer; Lihong He; Gary Breton; Michael L Dansinger; Ben Saida; Chong Yuan

    doi:10.1101/2021.01.19.21249604 Date: 2021-01-20 Source: medRxiv

    Most deaths MESHD from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection MESHD occur in older subjects. We assessed age effects and clinical utility of serum SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies and serum inflammatory markers. Serum IgG, IgM, and neutralizing antibody levels were measured using chemiluminescence assays from Diazyme (Poway, CA), while serum interleukin-6 HGNC ( IL-6 HGNC), C reactive protein HGNC ( CRP HGNC), and ferritin were measured with immunoassays obtained from Roche (Indianapolis, IN). In 79,005 subjects, IgG and IgM levels were positive ([≥]1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively. In antibody positive subjects, median IgG levels were 3.93 AU/mL if <45 years of age, 10.18 AU/mL if 45-64 years of age, and 10.85 AU/mL if [≥]65 years of age (p<0.0001). In SARS-CoV-2 RNA positive cases, family members and exposed subjects (n=1,111), antibody testing was found to be valuable for case finding, and persistent IgM levels were associated with chronic symptoms. In non-hospitalized and hospitalized subjects assessed for SARS-CoV-2 RNA (n=278), median IgG levels in AU/mL were 0.05 in negative subjects (n=100), 14.83 in positive outpatients (n=129), and 30.61 in positive hospitalized patients (n=49, p<0.0001). Neutralizing antibody levels correlated significantly with IgG (r=0.875; p<0.0001). Two or more of the criteria of IL-6 HGNC [≥]10 pg/mL, CRP HGNC [≥]10 mg/L, and/or IgM >1.0 AU/mL occurred in 97.7% of inpatients versus 1.8% of outpatients (>50-fold relative risk, C statistic 0.986, p<0.0001). Our data indicate that: 1) IgG levels are significantly higher in positive older subjects, possibly to compensate for decreased cellular immunity with aging; 2) IgG levels are important for case finding in family clusters; 3) IgG levels are significantly correlated with neutralizing antibody levels; 4) persistently elevated IgM levels are associated with chronic disease MESHD; and 5) markedly elevated IL-6 HGNC, hs- CRP HGNC, and/or positive IgM accurately identify SARS-CoV-2 RNA positive subjects requiring hospitalization.

    Network Representation Learning-Based Drug Mechanism Discovery and Anti-Inflammatory Response Against COVID-19 MESHD

    Authors: Wang Xiaoqi; Bin Xin; Zhijian Xu; Kenli LI; Fei Li; Wu Zhong; Weihong Tan; Shaoliang Peng

    doi:10.26434/chemrxiv.12531314.v3 Date: 2021-01-18 Source: ChemRxiv

    Recent studies have been demonstrated that the excessive inflammatory response is an important factor of death in COVID-19 MESHD patients. In this study, we proposed a network representation learning-based methodology, termed AIdrug2cov, to discover drug mechanism and anti-inflammatory response for patients with COVID-19 MESHD. This work explores the multi-hub characteristic of a heterogeneous drug network integrating 8 unique networks. Inspired by the multi-hub characteristic, we design three billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Using the representation vectors, AIdrug2cov identifies 40 potential targets and 22 high-confidence drugs that bind to tumor necrosis factor(TNF)-α HGNC tumor necrosis factor(TNF)-α MESHD or interleukin(IL)-6 HGNC to prevent excessive inflammatory responses in COVID-19 MESHD patients. Finally, we analyze mechanisms of action based on PubMed publications and ongoing clinical trials, and explore the possible binding modes between the new predicted drugs and targets via docking program. In addition, the results in 5 pharmacological application suggested that AIdrug2cov significantly outperforms 5 other state-of-the-art network representation approaches, future demonstrating the availability of AIdrug2cov in drug development field. In summary, AIdrug2cov is practically useful for accelerating COVID-19 MESHD therapeutic development. The source code and data can be downloaded from https://github.com/pengsl-lab/AIdrug2cov.git.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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