Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ZLOCY)

• DOT Name: 2'-5'-oligoadenylate synthase 1 (OAS1)
• Synonyms: (2-5')oligo(A) synthase 1; 2-5A synthase 1; EC 2.7.7.84; E18/E16; p46/p42 OAS
• Gene Name: OAS1
• Related Disease:
  Multiple sclerosis
  Non-insulin dependent diabetes
  Anemia
  Autoimmune disease
  Chikungunya virus infection
  Cystic fibrosis
  Desmoid tumour
  Hand, foot and mouth disease
  Hepatitis B virus infection
  Hepatitis C virus infection
  Influenza
  Liver cirrhosis
  Melanoma
  Neoplasm
  Pulmonary alveolar proteinosis with hypogammaglobulinemia
  rubella
  Severe acute respiratory syndrome (SARS)
  Sjogren syndrome
  Systemic lupus erythematosus
  Tuberculosis
  Type-1 diabetes
  Prostate cancer
  Prostate carcinoma
• UniProt ID: OAS1_HUMAN
• PDB ID: 4IG8
• EC Number: 2.7.7.84
• Pfam ID: PF01909 ; PF10421
• Sequence:
  MMDLRNTPAKSLDKFIEDYLLPDTCFRMQINHAIDIICGFLKERCFRGSSYPVCVSKVVK
  GGSSGKGTTLRGRSDADLVVFLSPLTTFQDQLNRRGEFIQEIRRQLEACQRERAFSVKFE
  VQAPRWGNPRALSFVLSSLQLGEGVEFDVLPAFDALGQLTGGYKPNPQIYVKLIEECTDL
  QKEGEFSTCFTELQRDFLKQRPTKLKSLIRLVKHWYQNCKKKLGKLPPQYALELLTVYAW
  ERGSMKTHFNTAQGFRTVLELVINYQQLCIYWTKYYDFKNPIIEKYLRRQLTKPRPVILD
  PADPTGNLGGGDPKGWRQLAQEAEAWLNYPCFKNWDGSPVSSWILLAESNSADDETDDPR
  RYQKYGYIGTHEYPHFSHRPSTLQAASTPQAEEDWTCTIL
• Function: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L; [Isoform p46]: When prenylated at C-terminal, acts as a double-stranded RNA (dsRNA) sensor specifically targeted to membranous replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells where it binds to dsRNA structures in the SARS-CoV-2 5'-UTR and initiates a potent block to SARS-CoV-2 replication. Recognizes short stretches of dsRNA and activates RNase L. The binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5'- untranslated region (UTR) constituting the principal viral target. The same mechanism is necessary to initiate a block to cardiovirus EMCV ; [Isoform p42]: Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
• Tissue Specificity: Expressed in lungs.
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Hepatitis C (hsa05160)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Coro.virus disease - COVID-19 (hsa05171)
• Reactome Pathway:
  OAS antiviral response (R-HSA-8983711)
  Interferon alpha/beta signaling (R-HSA-909733)
  Interferon gamma signaling (R-HSA-877300)
• BioCyc Pathway: MetaCyc:ENSG00000089127-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Multiple sclerosis	DISB2WZI	Definitive	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Anemia	DISTVL0C	Strong	Genetic Variation	[3]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[4]
Chikungunya virus infection	DISDXEHY	Strong	Genetic Variation	[5]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[6]
Desmoid tumour	DISGX357	Strong	Altered Expression	[7]
Hand, foot and mouth disease	DISKJHLL	Strong	Genetic Variation	[8]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[9]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[10]
Influenza	DIS3PNU3	Strong	Altered Expression	[11]
Liver cirrhosis	DIS4G1GX	Strong	Genetic Variation	[12]
Melanoma	DIS1RRCY	Strong	Altered Expression	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Pulmonary alveolar proteinosis with hypogammaglobulinemia	DISOHFOR	Strong	Autosomal dominant	[15]
rubella	DISXUI9P	Strong	Genetic Variation	[16]
Severe acute respiratory syndrome (SARS)	DISYW14W	Strong	Genetic Variation	[17]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[9]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[18]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[19]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[20]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[21]
Prostate carcinoma	DISMJPLE	Limited	Genetic Variation	[21]

35 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[22]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[23]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[24]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[25]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[27]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[28]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[29]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[30]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[31]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[32]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[33]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[34]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[35]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[36]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[37]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[38]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[39]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[34]
Aspirin	DM672AH	Approved	Aspirin increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[40]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[34]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[41]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[34]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[34]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[42]
Interferon alfa-2B	DMWCQP4	Approved	Interferon alfa-2B increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[43]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[44]
Rigosertib	DMOSTXF	Phase 3	Rigosertib decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[47]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[48]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[50]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[51]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[52]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of 2'-5'-oligoadenylate synthase 1 (OAS1).	[53]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 2'-5'-oligoadenylate synthase 1 (OAS1).	[49]

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