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Pharmatab 014.Pdf NEWS LETTER . JUNE 2020 .VOLUME 1 . ISSUE 14 Bharathi Priya K, Shailaja K, Leena Muppa, Magimai Upagara Valan UPDATES ON DRUG TARGETS FOR SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2) Dr. S.Parasuraman, Associate Professor & Unit Head Pharmacology, AIMST University, Bedong, Malaysia Viruses are obligate intracellular parasites negative regulator of the RAAS system other antivirals, chloroquine is in phase I and and they do not carry out metabolic (downregulation of ACE2 directly affects phase II trials[5]. processes. Viruses utilize most of the cardiovascular function)[2] ACE2 inhibition The clinical eficacy of the enhanced platelet physiological machinery of the host and few induces ADAM17 gene expression, leading to inhibition, trypsin inhibitor, monoclonal drugs inhibiting viral replication without the release of tumor necrosis factor α (TNFα) antibodies, immunomodulator, Natural killer affecting the host cells. and cytokines such as interleukin 4 (IL-4) and cells, an immunosuppressive drug, and In 2019, Severe acute respiratory syndrome interferon γ (IFNγ); [3] increased cytokine vaccine also under the investigation. Globally, coronavirus 2 (SARS-CoV-2) is identiied concentrations activate further pro- about 3.4% of COVID-19 cases have died, and which is positive-sense single-stranded inlammatory pathways, leading to a cytokine the disease spreading can be prevented by ribonucleic acid (RNA) virus. SARS-CoV-2 is storm and [4] personal hygiene and by social distancing to the strain of beta-coronavirus which causes ADAM-17 also promotes the cleavage of ACE2 break the COVID chain. coronavirus disease 2019 (COVID-19), receptors. Anti-coronavirus therapies divided References: responsible for the COVID-19 pandemic. into two categories depending on the target 1.Cascella M, Rajnik M, Cuomo A, Dulebohn About 80% of SARS-CoV-2 infections are mild viz., [1] innate immune system response and, [2] SC, Di Napoli R. Features, Evaluation, and or asymptomatic, 15% of infections are blocking the signal pathways of human cells Treatment Coronavirus (COVID-19). severe (requiring oxygen therapy) and 5% of required for virus replication. Currently, Available in https://www.ncbi.nlm.nih.gov infections are critical that required intensive antiviral drugs (remdesivir, avifavir, /books/NBK55 4776/ [Last accessed on care [1]. a n d f a v i p i r a v i r ) , f u s i o n i n h i b i t o r 06-06-2020] SARS-CoV-2 contains four structural proteins (chloroquine), and adjuvant therapies are 2.Interim Clinical Guidance for Management including spike (S) protein, envelope (E) usedfor the management of COVID-19 o f P a t i e n ts with Conirmed Coronavirus protein, membrane (M) protein, and pandemic. Azithromycin and corticosteroid Disease (COVID-19) Available in https:// nucleocapsid (N) protein. It attaches to the ( d exa m e t h a s o n e ) a l s o u s e d fo r t h e www.cdc.gov /coronavirus/2019- host cell by binding its 'S protein' to the management of COVID-19. ncov/hcp/clinical-guidance-management- receptor protein, angiotensin-converting Camostat, Serine protease inhibitor is also one patients.html [Last accessed on 07-06- enzyme 2 (ACE2). ACE2 is expressed by of the targets for SARS-CoV2 which is under 2020] epithelial cells of the intestine, kidney, blood investigation. Convalescent plasma (plasma 3.COVID-19. Available in https://www. vessels, and, most abundantly, in type II exchange from the patients who have lecturio.com/covid-19-coronavirus- alveolar cells of the lungs. The human recovered from the virus infection) also used disease-2019/ [Last accessed on 07-06- enzyme transmembrane protease, serine 2 in some cases to reduce the severity of the 2020] (TMPRSS2), is also used by the virus for S infection. 4. Rabi FA, Al Zoubi MS, Kasasbeh GA, Salameh protein priming and to aid in membrane Globally, 778 clinical trials registered are DM, Al-Nasser AD. SARS-CoV-2 and fusion. The virus then enters the host cell via registered in USFDA (as on 07-06-2020) in coronavirus disease 2019: what we know endocytosis. that few drugs are under phase III trial (e.g.: so far. Pathogens 2020;9(3):231. SARS-CoV-2 affects the expression and ACT COVID19 trail). The drugs including 5.https://clinicaltrials.gov/ [Last accessed on presentation of ACE2, contributing to its lopinavir/ ritonavir, ribavirin, and IFN-beta 07-06-2020] pathogenesis by [1] reduced availability c o m bination, lopinavir /ritonavir, and on the cell surface because ACE2 is a int erf er on beta-1b, methylprednisolone with News Letter. June 2020 01 HISTORY OF CORONAVIRUS Mrs.K.Shailaja, Assistant Professor Coronavirus was irst described in 1932 in 2012 in Saudi Arabia with the Middle References: [2] 1. Kahn JS, Mclntosh K. History and and Human Coronavirus was irst East Respiratory Syndrome (MERS) In recent advances in coronavirus identiied in the year 1960s and found to December 2019, Chinese government discovery. Pediatr Infect Dis J. cause upper respiratory tract infections in informed world health organization about 2005;24(11):223-7. c h i l d re n . At l e a s t 5 n e w H u m a n the Novel strain of Coronavirus causing 2. Wertheim JO, Chu DWK, Peiris JSM, Coronavirus has been identiied yet 2003, severe illness named SARS-COV-2, and in Pond SLK, Poon LLM. A case for the which causes signiicant mortality and February 2020 nearly 1,67,500 COVID-19 ancient origin of coronaviruses. J Virol morbidity [1] Coronaviruses is not a single c a s e s h a v e b e e n i d e n t i i e d a n d 2013;87(12):7039-7045. virus it is a group of zoonotic viruses, documented. The virus has killed 6600 3. Andersen KG, Rambaut A, Lipkin WL, classiied into four types, of which Alpha people. Day to day the numbers go on Holmes EC, Garry RF. The proximal and Beta Coronaviruses was found increasing worldwide because of humans origin of SARS-COV-2. Nat Med 2020; exclusively in mammals and Gamma and to human transmission after a single 26, 450–452. Delta Coronaviruses infect the birds. It can introduction into the human population. cause illness ranging from the common The evidence shows that the virus evolved cold to severe respiratory diseases among to its current pathogenic state through the population. Zoonotic means the natural selection in a non-human host and viruses can be transmitted from animals to then enters into humans or else a non- humans. The irst known Coronavirus that pathogenic virus transmitted from animal caused severe illness in china by the year host into humans and then evolved into a 2003 is Severe Acute Respiratory pathogenic state within the human Syndrome (SARS). Second outbreak began population [3]. BASIC STRUCTURE AND CLASSIFICATION OF CORONA VIRUS Dr. Leena Paavitha, Assistant Professor Coronaviruses are a serious health threat their genomes. They are the Spike (K) virion membrane through the C-terminal to humans and other animals. They are a Membrane, Membrane (M), Envelope (E) trans-membrane and they interact with diverse family of viruses causing a wide Glycoprotein, Hemagglutinin Esterase the M proteins and the Virions get bound variety of diseases in both mammals and (HE), and Nucleocapsid (N) protein. All to the speciic surface receptors in the birds starting from enteritis to upper these envelope proteins and N protein plasma membrane of the host cell through respiratory diseases potentially lethal to are present in cell virions but HE the N-t erminus of the S proteins. humans by affecting their respiratory ( H e m a g g l u t i n i n - a c e t y l e s t e r a s e Membrane (M) glycoprotein: The M- system. These viruses are a large family g lyc oprotein) is present in a few beta proteins are glycosylated in the Golgi of RNA viruses. The typical generic coronaviruses. a p p a r a t u s a n d t h e y h a v e t h r e e coronavirus genome is a single strand of Spike (S) glycoprotein: they are located t r a n s m e m b r a n e r e g i o n s . T h e s e RNA and it is considered as the largest RNA outside the virion and it gives a typical modiications of the M-protein are virus genome [1]. shape and so they form a homotrimer, essential for the virion to fuse into the cell Genome Structure of Corona Virus [1,2] which resembles the formation of sun-like and it produces antigenic protein. The M- Coronavirus which is 100-160 nm in size is morphologies and that is why it is called protein plays a crucial role in the encoded with ive structural proteins in “Coronavirus”. S glycoproteins bind to the regeneration of the virions in the cell. 02 News Letter. June 2020 Envelope (E) glycoprotein: are small Envelope (E) glycoprotein: are small H e m a g g l u t i n i n - a c e t y l e s t e ra s e proteins that are composed of over 76 to 109 proteins that are composed of over 76 to 109 glycoprotein (HE): is a dimer trans- amino acids. These amino-acids in the N- amino acids. These amino-acids in the N- membrane protein that binds to the sugar terminus of the E-proteins allow attachment terminus of the E-proteins allow attachment moieties on the cell membranes.
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