Life Sciences Commons^™

Exploration Of Dark Chemical Genomics Space Via Portal Learning: Applied To Targeting The Undruggable Genome And Covid-19 Anti-Infective Polypharmacology, Tian Cai, Li Xie, Muge Chen, Yang Liu, Di He, Shuo Zhang, Cameron Mura, Philip Boume, Lei Xie

Publications and Research

Advances in biomedicine are largely fueled by exploring uncharted territories of human biology. Machine learning can both enable and accelerate discovery, but faces a fundamental hurdle when applied to unseen data with distributions that differ from previously observed ones—a common dilemma in scientific inquiry. We have developed a new deep learning framework, called Portal Learning , to explore dark chemical and biological space. Three key, novel components of our approach include: (i) end-to-end, step-wise transfer learning, in recognition of biology’s sequence-structure-function paradigm, (ii) out-of-cluster meta-learning, and (iii) stress model selection. Portal Learning provides a practical solution to the out-of-distribution (OOD) …

A Comparison Of The Evolution, Structure, And Function Of Sars-Cov And Sars-Cov-2 Spike Proteins, Tai Michaels

The Yale Undergraduate Research Journal

As the COVID-19 pandemic has developed into the largest pandemic of the twenty-first century, it has become apparent that this disease, caused by the SARS-CoV-2 virus, is unlike anything the modern world has faced before. Not only has the disease infected more than 16 million people worldwide, but its rapid spread has drawn global attention to the gaps in our understanding of its pathogenesis and the development of vaccines and treatments. One of the most important topics of research in the disease is the viral spike (S) protein which facilitates binding and entering host cells and plays a key role …

The Size And Culturability Of Patient-Generated Sars-Cov-2 Aerosol, Joshua L. Santarpia, Vicki L. Herrera, Danielle N. Rivera, Shanna Ratnesar-Shumate, St. Patrick Reid, Daniel N. Ackerman, Paul Denton, Jacob W.S. Martens, Ying Fan, Nicholas Conoan, Michael V. Callahan, James V. Lawler, David M. Brett-Major, John J. Lowe

Biology Faculty Publications

Background

Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission.

Objective

We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020.

Methods

Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Rapamycin And Metformin In Treating Covid-19, Avrohom Karp

The Science Journal of the Lander College of Arts and Sciences

The SARS-CoV-2 virus has spread rapidly, resulting in a global pandemic. There is a great need for an effective drug cocktail therapy to combat Acute Respiratory Distress Syndrome (ARDS), a major cause of death due to COVID-19. The two drugs examined are metformin, an antidiabetic medication, and rapamycin. Rapamycin is often prescribed for transplant patients as it has an immunosuppressive effect. The aim of the investigation was to determine the efficacy of metformin and rapamycin in treating COVID-19, and to examine what an effective protocol would look like. These two drugs both inhibit mTOR and can reduce the body’s auto-immune …

An Update Comprehensive Review On The Status Of Covid-19: Vaccines, Drugs, Variants And Neurological Symptoms, Ebru Özkan Oktay, Sali̇h Tuncay, Tuğba Kaman, Ömer Faruk Karasakal, Öznur Özge Özcan, Tuğçe Soylamiş, Mesut Karahan, Muhsi̇n Konuk

Turkish Journal of Biology

Various recently reported mutant variants, candidate and urgently approved current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many current situations with severe neurological damage and symptoms as well as respiratory tract disorders have begun to be reported. In particular, drug, vaccine, and neutralizing monoclonal antibodies (mAbs) have been developed and are currently being evaluated in clinical trials. Here, we review lessons learned from the use of novel mutant variants of the COVID-19 virus, immunization, new drug solutions, and antibody therapies for infections. Next, we focus on the B 1.1.7, B 1.351, P.1, and B.1.617 lineages or variants of …

Host Variations In Sars-Cov-2 Infection, Doruk Altiok, Eli̇f Zeynep Savci, Büşra Özkara, Kami̇l Alkan, Di̇lara Sultan Namdar, Gi̇zem Tunçer, Buğrahan Regai̇p Kilinç, Evren Sui̇çmez, Güneysu Çeti̇n, Si̇nan Ünal, Beyza Dönmüş, Zeynep Yağmur Karagülleoğlu, Di̇lrüba Beyza Uncuoğlu, Cansu Tekeli̇, Hani̇fe Ayşegül Mendi̇

Turkish Journal of Biology

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the zoonotic pathogen that causes the "Coronavirus Disease of 2019 (COVID-19)", and COVID-19 itself is yet to be thoroughly understood. Both the disease as well as the mechanisms by which the host interacts with the SARS-CoV-2 have not been fully enlightened. The epidemiological factors -e.g. age, sex, race-, the polymorphisms of the host proteins, the blood types and individual differences have all been in discussions about affecting the progression and the course of COVID-19 both individually and collectively, as their effects are mostly interwoven. We focused mainly on the effect of …

Ss-Carboline Alkaloids Induce Structural Plasticity And Inhibition Of Sars-Cov-2 Nsp3 Macrodomain More Potently Than Remdesivir Metabolite Gs-441524: Computational Approach, Yusuf Oloruntoyin Ayipo, Sani Najib Yahaya, Halimah Funmilayo Babamale, Iqrar Ahmad, Harun Patel, Mohd Nizam Mordi

Turkish Journal of Biology

The nsp3 macrodomain is implicated in the viral replication, pathogenesis and host immune responses through the removal of ADP-ribosylation sites during infections of coronaviruses including the SARS-CoV-2. It has ever been modulated by macromolecules including the ADP-ribose until Ni and co-workers recently reported its inhibition and plasticity enhancement unprecedentedly by remdesivir metabolite, GS-441524, creating an opportunity for investigating other biodiverse small molecules such as ß-Carboline (ßC) alkaloids. In this study, 1497 ßC analogues from the HiT2LEAD chemical database were screened, using computational approaches of Glide XP docking, molecular dynamics simulation and pk-CSM ADMET predictions. Selectively, ßC ligands, 129, 584, 1303 …

Cannabinoids For Sars-Cov-2 And Is There Evidence Of Their Therapeutic Efficacy?, Ahmet Onay, Abdulselam Ertaş, Veysel Süzerer, İsmai̇l Yener, Mustafa Abdullah Yilmaz, Emi̇ne Ayaz Ti̇lkat, Remzi̇ Eki̇nci̇, Nesri̇n Bozhan, Sevgi̇ İrtegün

Turkish Journal of Biology

To combat the coronaviruses and their novel variants, therapeutic drugs and the development of vaccines that are to be effective throughout human life are urgently needed. The endocannabinoid system (ECS) acts as a modulator in the activation of the microcirculation, immune system, and autonomic nervous system, along with controlling pharmacological functions such as emotional responses, homeostasis, motor functions, cognition, and motivation. The ECS contains endogenous cannabinoids, cannabinoid receptor (CBRs), and enzymes that regulate their biosynthesis, transport, and degradation. Moreover, phytocannabinoids and synthetic cannabinoids that mimic the action of endocannabinoids also play an essential role in the modulation of the ECS. …

Pathogenesis And Treatment Of Cytokine Storm In Covid-19, Mehmet Soy, Gökhan Keser, Mehmet Pami̇r Atagündüz

Turkish Journal of Biology

COVID-19 is a viral infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that killed a large number of patients around the world. A hyperinflammatory state resulting in a cytokine storm and adult respiratory distress syndrome seems to be the major cause of the death. Many mechanisms have been suggested in the pathogenesis of COVID-19 associated cytokine storm (COVID-CS). Insufficient viral clearance and persistence of a strong cytokine response despite inadequate antiviral immunity seem to be the main mechanisms underlying the pathogenesis. The diagnosis of COVID-19 is based on relatively constant clinical symptoms, clinical findings, laboratory tests, and …

Current Mutatome Of Sars-Cov-2 In Turkey Reveals Mutations Of Interest, Doğa Eski̇er, Evren Akalp, Özlem Dalan, Gökhan Karakülah, Yavuz Oktay

Turkish Journal of Biology

As the underlying pathogen for the COVID-19 pandemic that has affected tens of millions of lives worldwide, SARS-CoV-2 and its mutations are among the most urgent research topics worldwide. Mutations in the virus genome can complicate attempts at accurate testing or developing a working treatment for the disease. Furthermore, because the virus uses its own proteins to replicate its genome, rather than host proteins, mutations in the replication proteins can have cascading effects on the mutation load of the virus genome. Due to the global, rapidly developing nature of the COVID-19 pandemic, local demographics of the virus can be difficult …

Genomic Chronicle Of Sars-Cov-2: A Mutational Analysis With Over 1 Million Genome Sequences, Osman Mutluhan Uğurel, Oğuz Ata, Di̇lek Balik

Turkish Journal of Biology

Use of information technologies to analyse big data on SARS-CoV-2 genome provides an insight for tracking variations and examining the evolution of the virus. Nevertheless, storing, processing, alignment and analyses of these numerous genomes are still a challenge. In this study, over 1 million SARS-CoV-2 genomes have been analysed to show distribution and relationship of variations that could enlighten development and evolution of the virus. In all genomes analysed in this study, a total of over 215M SNVs have been detected and average number of SNV per isolate was found to be 21.83. Single nucleotide variant (SNV) average is observed …

Targeting Cov-2 Spike Rbd And Ace-2 Interaction With Flavonoids Of Anatolian Propolis By In Silico And In Vitro Studies In Terms Of Possible Covid-19 Therapeutics, Hali̇l İbrahi̇m Güler, Fulya Ay Şal, Zehra Can, Yakup Kara, Oktay Yildiz, Ali̇ Osman Beldüz, Sabri̇ye Çanakçi, Sevgi̇ Kolayli

Turkish Journal of Biology

Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 …

In Silico Drug Repositioning Against Human Nrp1 To Block Sars-Cov-2 Host Entry, Şeref Gül

Turkish Journal of Biology

Despite COVID-19 turned into a pandemic, no approved drug for the treatment or globally available vaccine is out yet. In such a global emergency, drug repurposing approach that bypasses a costly and long-time demanding drug discovery process is an effective way in search of finding drugs for the COVID-19 treatment. Recent studies showed that SARS-CoV-2 uses neuropilin-1 (NRP1) for host entry. Here we took advantage of structural information of the NRP1 in complex with C-terminal of spike (S) protein of SARSCoV- 2 to identify drugs that may inhibit NRP1 and S protein interaction. U.S. Food and Drug Administration (FDA) approved …

Binary-Qsar Guided Virtual Screening Of Fda Approved Drugs And Compounds In Clinical Investigation Against Sars-Cov-2 Main Protease, Lalehan Oktay, Ece Erdemoğlu, İlayda Tolu, Yeşi̇m Yumak, Ayşenur Özcan, Eli̇f Acar, Şehri̇ban Büyükkiliç, Alpsu Olkan, Serdar Durdaği

Turkish Journal of Biology

With the emergence of the new SARS-CoV-2 virus, drug repurposing studies have gained substantial importance. Combined with the efficacy of recent improvements in ligand- and target-based virtual screening approaches, virtual screening has become faster and more productive than ever. In the current study, an FDA library of approved drugs and compounds under clinical investigation were screened for their antiviral activity using the antiviral therapeutic activity binary QSAR model of the MetaCore/MetaDrug platform. Among 6733-compound collection, we found 370 compounds with a normalized therapeutic activity value greater than a cutoff of 0.75. Only these selected compounds were used for molecular docking …

The Current State Of Validated Small Molecules Inhibiting Sars-Cov-2 Non-Structural Proteins, Fati̇h Kocabaş, Merve Uslu

Turkish Journal of Biology

The current COVID-19 outbreak has had a profound influence on public health and daily life. Despite all restrictions and vaccination programs, COVID-19 still can lead to fatality due to a lack of COVID-19-specific treatments. A number of studies have demonstrated the feasibility to develop therapeutics by targeting underlying components of the viral proteome. Here we reviewed recently developed and validated small molecule inhibitors of SARS-CoV-2's nonstructural proteins. We described the validation level of identified compounds specific for SARS-CoV-2 in the presence of in vitro and in vivo supporting data. The mechanisms of pharmacological activity, as well as approaches for developing …

The Potential Use Of Drosophila As An In Vivo Model Organism For Covid-19-Related Research: A Review, Eşref Demi̇r

Turkish Journal of Biology

The world urgently needs effective antiviral approaches against emerging viruses, as shown by the coronavirus disease 2019 (COVID-19) pandemic, which has become an exponentially growing health crisis. Scientists from diverse backgrounds have directed their efforts towards identifying key features of SARS-CoV-2 and clinical manifestations of COVID-19 infection. Reports of more transmissible variants of SARS-CoV-2 also raise concerns over the possibility of an explosive trajectory of the pandemic, so scientific attention should focus on developing new weapons to help win the fight against coronaviruses that may undergo further mutations in the future. Drosophila melanogaster offers a powerful and potential in vivo …