3C-like proteinase Google Drive Data

Gray amino acids fall below the average conservation (value <0) for each protein, yellow = 0-0.5, light orange = 0.5-1, orange = 1-1.5, dark orange = 1.5-2, red = >2

Cysteine-like protease (3CLpro) (Mpro) (nsp5)– the 3D structure of 3CLpro of SARS-CoV-2 is very similar to SARS-CoV with a sequence identity of >96%.7 3CLpro is responsible for all cleavage events not mediated by PLpro, it cleaves nsp4-16. It recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. The protease is also able to bind an ADP-ribose-1”-phosphate (ADRP).2 3CLpro also interferes with localization of some proteins. Wild-type 3CLpro inhibits histone deacetylase 2 (HDAC2) transport into the nucleus, potentially impacting mediation of inflammation and interferon response. 3CLpro (C145A) interferes with tRNA methyltransferase 1 (TRMT1). TRMT1 is cleaved by 3CLpro, removing its zinc finger and nuclear localization signal and likely resulting in an exclusively mitochondrial localization. TRMT1 is responsible for synthesis of the dimethylguanosine (m2,2G) base modification on both nuclear and mitochondrial tRNAs40.8 3CLpro is a promising target for anti-coronaviral drugs. One study found that Cobicistat and Amprenavir bind to the protease effectively. Amprenavir’s prodrug version is called Fosamprenavir, and is currently used in treating HIV. The study recommended Fosamprenavir be considered as a potential treatment for SARS-CoV-2.9 Another study identified compound 621 from Asinex Focused Covalent Library as well as Paritaprevir and Simeprevir from FDA-approved protease inhibitors as potential inhibitors of 3CLpro. 10 Antivirals ledipasvir and velpatasvir are attractive therapeutics as well. Based on an in silico study, 2-deoxy-D-glucose can inactivate 3CLpro and nsp15 endoribonuclease.11

3C-like proteinase 3,397 Sequences

Amino AcidAAAAConservationConservation Z-scoreRMSD_CARMSF[A]Secondary StructureDCCM >0.9
3264SSER56.553755520.1921788882.7491.574C0
3265GGLY99.734904271.4330666962.3510.967C0
3266FPHE25.09572901-0.7118239632.0780.96C0
3267RARG37.58468336-0.3529314452.8660.844C1
3268KLYS95.405007361.3086393383.2751.06C1
3269MMET78.9101620.8346303523.7661.325C0
3270AALA44.00589102-0.1684065192.3370.899C0
3271FPHE11.51693667-1.1020349311.0441.732C0
3272PPRO99.793814431.4347595861.5711.329C0
3273SSER85.655375551.0284661691.7191.449C0
3274GGLY70.279823270.586622082.5861.636C0
3275KLYS23.00441826-0.771921532.6972.386C0
3276VVAL97.643593521.3729691292.4071.662C0
3277EGLU99.823269511.435606032.231.229C0
3278GGLY10.0736377-1.1435107172.2180.943C0
3279CCYS99.734904271.4330666961.9320.923E0
3280MMET35.52282769-0.4121825681.6410.867E0
3281VVAL99.764359351.4339131411.4030.983E0
3282QGLN32.57731959-0.496827031.4461.273E1
3283VVAL99.734904271.4330666961.1591.081E2
3284TTHR47.27540501-0.0744511661.3361.134E2
3285CCYS32.69513991-0.4934412521.7021.215E1
3286GGLY80.117820320.8693345824.041.525T0
3287TTHR9.484536082-1.160439613.5291.953T0
3288TTHR17.5257732-0.9293602291.7491.483E1
3289TTHR49.07216495-0.0228180451.4741.277E2
3290LLEU99.823269511.435606031.251.523E1
3291NASN99.823269511.435606031.1420.776E0
3292GGLY99.734904271.4330666961.1060.723E0
3293LLEU90.574374081.169822421.2570.898E1
3294WTRP99.852724591.4364524751.1710.833E1
3295LLEU98.468335791.3966695781.631.009E0
3296DASP48.07069219-0.0515971621.4221.277T0
3297DASP71.458026510.6204798641.1961.101T0
3298VVAL6.715758468-1.2400054041.1351.213E0
3299VVAL84.624447720.9988406080.770.958E0
3300YTYR48.12960236-0.0499042720.8120.876E0
3301CCYS99.558173781.4279880290.9371.007E0
3302PPRO99.852724591.4364524750.8560.983C0
3303RARG99.852724591.4364524751.3331.417G0
3304HHIS99.823269511.435606031.8652.13G1
3305VVAL98.880706921.4085198021.3161.482G1
3306IILE58.055964650.2353475641.5981.642G0
3307CCYS46.92194404-0.0846085021.8141.83C1
3308TTHR9.337260677-1.1646718332.5842.099T2
3309SSER25.56701031-0.6982808492.6262.262T2
3310EGLU9.366715758-1.1638253882.2852.384T2
3311DASP21.79675994-0.806625761.8471.826T1
3312MMET23.03387334-0.7710750861.9872.46C0
3313LLEU12.81296024-1.0647913681.9172.53C0
3314NASN20.14727541-0.8540266582.5672.896C0
3315PPRO46.9808542-0.0829156122.8573.233C0
3316NASN32.57731959-0.496827033.4682.939H0
3317YTYR80.206185570.8718739152.9642.66H1
3318EGLU14.93372607-1.0038473553.1953.158H1
3319DASP25.03681885-0.7135168522.5452.324H0
3320LLEU46.95139912-0.0837620572.4462.153H0
3321LLEU82.650957290.9421288192.1172.266H0
3322IILE31.7820324-0.5196810352.1672.195H0
3323RARG23.62297496-0.7541461942.2133.083H1
3324KLYS10.16200295-1.1409713832.2231.802C1
3325SSER9.484536082-1.160439612.1641.671T0
3326NASN49.01325479-0.0245109341.5581.34T1
3327HHIS78.556701030.8244730171.6982.007T2
3328NASN34.87481591-0.430804352.0481.449T1
3329FPHE99.52871871.4271415841.3331.329C0
3330LLEU9.278350515-1.1663647221.2331.576E0
3331VVAL69.337260680.5595358521.1191.235E0
3332QGLN32.60677467-0.4959805851.7991.377E0
3333AALA9.690721649-1.1545144971.6291.235E0
3334GGLY41.14874816-0.2505116472.3611.77T0
3335NASN50.780559650.0262757433.573.205T0
3336VVAL50.780559650.0262757432.1461.936E0
3337QGLN13.04860088-1.0580198111.9972.172E0
3338LLEU99.234167891.4186771381.2091.23E0
3339RARG33.28424153-0.4765123591.1652.001E1
3340VVAL99.469808541.4254486951.111.298E2
3341IILE11.75257732-1.0952633741.3261.305E2
3342GGLY57.407952870.2167257821.351.163E3
3343HHIS33.28424153-0.4765123591.2761.507E2
3344SSER11.95876289-1.0893382621.2951.479E2
3345MMET78.468335790.8219336831.4241.835E1
3346QGLN40.97201767-0.2555903142.1261.969E1
3347NASN9.278350515-1.1663647221.8851.359T2
3348CCYS22.06185567-0.7990077581.2271.109T2
3349VVAL20.4712813-0.8447157681.0191.06E1
3350LLEU99.675994111.4313738071.0021.644E1
3351KLYS29.27835052-0.5916288271.0341.531E1
3352LLEU71.840942560.6314836441.0341.209E1
3353KLYS41.00147275-0.254743871.0981.67E3
3354VVAL84.477172310.9946083850.9291.102E2
3355DASP33.10751105-0.4815910271.1511.402C1
3356TTHR13.25478645-1.0520946991.1791.461C0
3357AALA38.20324006-0.3351561081.2121.243C1
3358NASN99.911634761.4381453641.2491.021T1
3359PPRO42.50368189-0.2115751941.4131.415T0
3360KLYS10.04418262-1.1443571623.4272.875T0
3361TTHR99.911634761.4381453642.4861.163T0
3362PPRO99.941089841.4389918092.561.086C0
3363KLYS59.057437410.2641266812.51.607E1
3364YTYR86.804123711.061477512.1071.071E2
3365KLYS34.37407953-0.4451939081.9271.498E2
3366FPHE81.85567010.9192748141.7291.302E2
3367VVAL17.23122239-0.9378246751.81.439E1
3368RARG13.69661267-1.0393980291.8251.362C0
3369IILE11.7820324-1.0944169291.5851.133C1
3370QGLN12.66568483-1.0690235911.3961.397T1
3371PPRO75.110456550.7254389971.2231.104T0
3372GGLY99.882179681.4372989191.1791.03T1
3373QGLN9.837997054-1.1502822741.3441.453E1
3374TTHR23.44624448-0.7592248611.5451.281E0
3375FPHE95.463917531.3103322271.2160.794E0
3376SSER33.60824742-0.4672014681.0850.849E0
3377VVAL46.48011782-0.0973051710.931.168E0
3378LLEU80.294550810.8744132491.1711.176E0
3379AALA79.852724590.861716581.2740.881E0
3380CCYS66.156111930.4681198331.5610.924E0
3381YTYR99.941089841.4389918091.5360.837E0
3382NASN47.06921944-0.0803762791.8781.468T0
3383GGLY99.882179681.4372989191.6381.073T0
3384SSER21.97349043-0.8015470921.910.976E0
3385PPRO55.287187040.155781771.720.917E0
3386SSER14.34462445-1.0207762482.0130.944E0
3387GGLY90.868924891.1782868671.2990.731E0
3388VVAL47.7466863-0.0609080521.0940.92E0
3389YTYR56.759941090.1981040.9320.817E0
3390QGLN9.307805596-1.1655182771.1391.132E0
3391CCYS9.896907216-1.1485893851.1870.945E0
3392AALA9.366715758-1.1638253880.9010.952E0
3393MMET88.247422681.1029532960.6590.972C0
3394RARG95.935198821.3238753410.7590.747T0
3395PPRO32.04712813-0.5120630331.1210.924T0
3396NASN79.204712810.8430947980.8370.79T0
3397FPHE5.449189985-1.2764025220.7860.954T0
3398TTHR95.905743741.3230288960.7950.813C0
3399IILE98.527245951.3983624670.8310.87C0
3400KLYS57.584683360.221804450.9931.082C0
3401GGLY79.970544920.8651023581.2550.833T0
3402SSER99.764359351.4339131411.320.993T0
3403FPHE99.823269511.435606031.1951.204T0
3404LLEU66.36229750.4740449451.070.874T0
3405NASN39.82326951-0.2886016542.2581.179C0
3406GGLY99.823269511.435606033.8990.991C0
3407SSER47.86450663-0.0575222743.3780.754C0
3408CCYS99.675994111.4313738071.1080.689C0
3409GGLY99.882179681.4372989191.1070.557E0
3410SSER99.764359351.4339131411.820.812E0
3411VVAL68.865979380.5459927381.4551.174E0
3412GGLY99.705449191.4322202521.0810.615E0
3413FPHE26.9808542-0.6576515071.1670.897E0
3414NASN50.250368190.011039742.0251.258E1
3415IILE34.87481591-0.430804352.8021.724E2
3416DASP9.513991163-1.1595931653.0191.819E2
3417YTYR9.307805596-1.1655182773.9453.06T2
3418DASP26.68630339-0.6661159533.8871.95T1
3419CCYS19.85272459-0.8624911042.4631.455E1
3420VVAL67.098674520.4952060612.1121.41E1
3421SSER9.337260677-1.1646718331.6921.106E0
3422FPHE95.758468341.3187966731.2950.805E0
3423CCYS55.434462440.1600139931.1461.005E0
3424YTYR99.764359351.4339131411.080.753E0
3425MMET77.349042710.7897687880.9610.886E0
3426HHIS99.705449191.4322202520.6810.64E0
3427HHIS35.8173785-0.4037181220.6940.839E0
3428MMET33.10751105-0.4815910270.8341.185E0
3429EGLU99.734904271.4330666961.0921.093E0
3430LLEU95.611192931.314564451.0811.113E1
3431PPRO25.68483063-0.694895071.5271.313T1
3432TTHR23.06332842-0.7702286411.2721.175T0
3433GGLY78.703976440.828705241.4621.17E0
3434VVAL9.837997054-1.1502822740.9251.182E0
3435HHIS99.617083951.4296809181.0080.91E0
3436AALA9.307805596-1.1655182770.7730.822E0
3437GGLY99.764359351.4339131410.6820.651E0
3438TTHR43.00441826-0.1971856360.8560.789E0
3439DASP66.50957290.4782771691.4290.904E0
3440LLEU49.955817380.0025752941.6591.346T0
3441EGLU18.79234168-0.8929631111.861.547T0
3442GGLY99.675994111.4313738071.5570.898E0
3443NASN11.34020619-1.1071135991.4581.248E1
3444FPHE43.29896907-0.1887211891.1090.965E1
3445YTYR99.764359351.4339131410.8240.789C0
3446GGLY99.764359351.4339131410.8590.852C0
3447PPRO27.33431517-0.6474941721.4821.072C0
3448FPHE41.91458027-0.2285040861.2930.909C0
3449VVAL22.68041237-0.7812324211.5381.381C0
3450DASP99.793814431.4347595862.0691.246C0
3451RARG10.51546392-1.1308140482.7592.387C0
3452QGLN46.95139912-0.0837620572.382.342C1
3453TTHR28.42415317-0.6161757212.1822.005C2
3454AALA25.24300442-0.707591742.2711.919C1
3455QGLN99.823269511.435606031.9691.113C0
3456AALA9.985272459-1.1460500511.5391.217T0
3457AALA10.04418262-1.1443571622.1891.502T0
3458GGLY36.4359352-0.3859427851.8731.432T0
3459TTHR37.0544919-0.3681674481.321.053T0
3460DASP63.151693670.3817824821.091.357C0
3461TTHR10.63328424-1.127428271.4351.216C0
3462TTHR11.19293078-1.1113458222.1431.052E0
3463IILE12.51840943-1.0732558142.5141.3H1
3464TTHR58.615611190.2514300112.420.94H1
3465VVAL41.97349043-0.2268111972.611.094H1
3466NASN99.793814431.4347595862.530.761H1
3467VVAL72.783505150.6585698721.9820.905H0
3468LLEU38.35051546-0.3309238851.8970.979H0
3469AALA98.409425631.3949766892.1990.868H0
3470WTRP63.917525770.4037900422.0410.895H0
3471LLEU97.938144331.3814335751.6970.872H0
3472YTYR99.646539031.4305273622.1450.772H1
3473AALA96.789396171.3484222352.5760.946H1
3474AALA95.699558171.3171037842.2210.928H1
3475VVAL10.81001473-1.1223496022.5181.104H2
3476IILE49.83799705-0.0008104853.2131.218H2
3477NASN79.675994110.8566379123.5261.259H1
3478GGLY66.391752580.474891393.3531.211C0
3479DASP14.28571429-1.0224691372.6411.185C0
3480RARG20.14727541-0.8540266583.0211.851T0
3481WTRP79.970544920.8651023583.0051.437T0
3482FPHE52.901325480.0872197562.0040.99T0
3483LLEU54.786450660.1413922111.6881.17T0
3484NASN9.867452135-1.149435831.391.694C0
3485RARG9.337260677-1.1646718331.9262.824C0
3486FPHE9.307805596-1.1655182772.0242.398C0
3487TTHR24.62444772-0.7253670772.2441.61C1
3488TTHR32.54786451-0.4976734752.2351.368C2
3489TTHR13.40206186-1.0478624762.3471.42H2
3490LLEU17.82032401-0.9208957832.7191.599H2
3491NASN9.572901325-1.1579002763.141.84H2
3492DASP41.11929308-0.2513580912.7941.517H2
3493FPHE73.549337260.6805774322.4251.346H2
3494NASN99.764359351.4339131412.8431.348H2
3495LLEU9.307805596-1.1655182773.0642.148H1
3496VVAL9.307805596-1.1655182772.5161.912H0
3497AALA98.9101621.4093662472.5211.351H0
3498MMET16.34756996-0.9632180143.2412.437H1
3499KLYS9.926362297-1.147742942.8922.46H1
3500YTYR10.0736377-1.1435107171.9861.693C0
3501NASN9.837997054-1.1502822743.1431.957E0
3502YTYR13.10751105-1.0563269222.551.267E1
3503EGLU9.337260677-1.1646718332.4311.267E1
3504PPRO19.23416789-0.8802664412.5521.223C0
3505LLEU14.93372607-1.0038473552.8411.518C0
3506TTHR10.30927835-1.136739163.4721.351H1
3507QGLN9.307805596-1.1655182773.8211.965H2
3508DASP9.602356406-1.1570538314.2511.489H2
3509HHIS9.278350515-1.1663647223.3671.1H2
3510VVAL9.307805596-1.1655182772.9291.23H2
3511DASP39.02798233-0.3114556593.6321.431H2
3512IILE9.189985272-1.1689040563.4161.359H2
3513LLEU13.75552283-1.037705143.0410.991H2
3514GGLY9.572901325-1.1579002763.3471.038H2
3515PPRO9.985272459-1.1460500513.6851.221H2
3516LLEU98.615611191.4009018013.0411.137H2
3517SSER28.77761414-0.6060183862.4321.058H2
3518AALA58.173784980.2387333423.0291.353H2
3519QGLN9.13107511-1.1705969453.3591.598H2
3520TTHR96.082474231.3281075642.6971.178H2
3521GGLY95.316642121.3061000042.2131.179H2
3522IILE10.19145803-1.1401249391.5411.285C1
3523AALA30.95729013-0.5433814841.5441.104H0
3524VVAL64.889543450.4317227151.7651.049H0
3525LLEU9.307805596-1.1655182771.6851.205H0
3526DASP9.248895434-1.1672111671.4730.964H1
3527MMET10.81001473-1.1223496021.4210.869H1
3528CCYS9.366715758-1.1638253881.6790.849H1
3529AALA46.65684831-0.0922265031.6671.096H2
3530SSER25.24300442-0.707591741.4681.018H1
3531LLEU10.0736377-1.1435107171.4641.2H1
3532KLYS23.97643594-0.7439888582.1061.695H1
3533EGLU8.483063328-1.1892187272.3351.551H1
3534LLEU83.41678940.9641363792.2361.768H2
3535LLEU9.955817378-1.1468964962.4541.844H2
3536QGLN10.04418262-1.1443571624.0782.773H1
3537NASN9.307805596-1.1655182774.2571.971H0
3538GGLY61.502209130.3343815842.7011.322C0
3539MMET9.337260677-1.1646718332.3991.667C0
3540NASN9.602356406-1.1570538312.0381.252C0
3541GGLY83.652430040.9709079361.2970.844C0
3542RARG28.27687776-0.6204079441.9281.258C0
3543TTHR18.05596465-0.9141242262.5551.156C0
3544IILE98.851251841.4076733581.9861.028T0
3545LLEU84.536082470.9963012742.3071.095T0
3546GGLY94.491899851.2823995552.3010.913T0
3547SSER49.66126657-0.0058891522.3681.155T0
3548AALA3.858615611-1.3221105313.4980.955C0
3549LLEU1.973490427-1.3762829871.9941.882C0
3550LLEU67.776141380.5146742871.2561.295C0
3551EGLU65.949926360.4621947211.3981.235C0
3552DASP95.758468341.3187966732.0680.777C0
3553EGLU95.611192931.314564452.7811.007C0
3554FPHE63.976435940.4054829323.5970.921C0
3555TTHR94.698085421.2883246674.0051.038H0
3556PPRO71.78203240.6297907553.890.955H1
3557FPHE9.42562592-1.1621324994.1771.429H2
3558DASP46.92194404-0.0846085024.0671.032H2
3559VVAL98.262150221.3907444653.4631.123H2
3560VVAL19.76435935-0.8650304383.8831.387H2
3561RARG33.46097202-0.4714336914.2872.063H2
3562QGLN99.410898381.4237558064.0821.374H2
3563CCYS9.42562592-1.1621324995.5521.593C1
3564SSER9.661266568-1.1553609426.5281.983C0
3565GGLY95.581737851.3137180055.3161.752C0
3566VVAL84.742268041.0022263866.5782.566C0
3567TTHR10.98674521-1.1172709348.74.059C1
3568FPHE8.983799705-1.17482916811.5715.853C2
3569QGLN94.815905741.29171044512.9046.502C1

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