ORF3a 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

ORF3a– acts as a viroporin and forms homotetrameric potassium sensitive ion channels. ORF3a up-regulates expression of fibrinogen subunits FGA, FGB and FGG in host lung epithelial cells.2 It also activates NLRP3 inflammasome.8 It downregulates the type 1 interferon receptor by inducing serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and increasing IFNAR1 ubiquitination. ORF3a also induces apoptosis in cell culture and may modulate virus release.2 The accumulation of mutations and polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread.28

3a 65 Sequences

Amino AcidAAAAConservationConservation Z-scoreRMSD_CARMSF[A]Secondary StructureDCCM >0.9
1MMET98.461538460.65838380614.1427.836C1
2DASP98.461538460.65838380611.745.835C1
3LLEU98.461538460.6583838069.5174.95C0
4FPHE98.461538460.6583838065.7874.9C0
5MMET95.384615380.5733212996.8463.095C0
6RARG52.30769231-0.6175538037.2252.817C0
7IILE70.76923077-0.1071787597.6273.79C0
8FPHE1000.700915068.1012.92C0
9TTHR1000.700915066.5044.524C0
10IILE6.153846154-1.8934914125.7113.765C0
11GGLY95.384615380.5733212996.3254.761C2
12TTHR10.76923077-1.7658976515.7364.321C2
13VVAL10.76923077-1.7658976515.0453.311C3
14TTHR98.461538460.6583838065.3544.805C2
15LLEU10.76923077-1.7658976514.5993.431C1
16KLYS10.76923077-1.7658976513.714.692C0
17QGLN10.76923077-1.7658976514.1813.726C0
18GGLY24.61538462-1.3831163684.9212.693C0
19EGLU10.76923077-1.7658976514.9213.219C0
20IILE95.384615380.5733212995.5372.635E0
21KLYS10.76923077-1.7658976515.6962.748E1
22DASP9.230769231-1.8084289054.9332.782C1
23AALA98.461538460.6583838065.6163.552C0
24TTHR10.76923077-1.7658976517.6714.947C1
25PPRO84.615384620.27560252411.3046.996C3
26SSER9.230769231-1.80842890511.27.542C2
27DASP9.230769231-1.8084289059.9164.731C2
28FPHE6.153846154-1.8934914127.3385.666C2
29VVAL93.846153850.5307900456.1762.861C2
30RARG13.84615385-1.6808351446.3285.798C2
31AALA95.384615380.5733212995.172.438E0
32TTHR98.461538460.6583838065.522.033E0
33AALA1000.700915065.3791.919E0
34TTHR95.384615380.5733212994.4341.796C0
35IILE1000.700915064.5362.106C0
36PPRO1000.700915066.1522.761C0
37IILE10.76923077-1.7658976515.2193.735C1
38QGLN1000.700915063.63.597C1
39AALA1000.700915063.7513.652C0
40SSER78.461538460.1054775094.3143.864C0
41LLEU86.153846150.3181337773.8613.83C0
42PPRO90.769230770.4457275383.1862.636C0
43FPHE1000.700915065.2144.337C1
44GGLY86.153846150.3181337773.442.067C1
45WTRP1000.700915063.3131.946C0
46LLEU1000.700915063.2681.143C0
47IILE16.92307692-1.5957726374.9091.601T0
48VVAL49.23076923-0.702616313.7721.469T0
49GGLY1000.700915063.5041.008T0
50VVAL1000.700915062.0481.337T0
51AALA1000.700915063.5941.292C0
52LLEU52.30769231-0.6175538032.2311.111T0
53LLEU1000.700915062.3731.105T0
54AALA98.461538460.6583838062.5681.25T0
55VVAL1000.700915062.4041.414T0
56FPHE1000.700915064.0361.205C0
57QGLN1000.700915066.1141.817C0
58SSER98.461538460.6583838066.4481.578C0
59AALA98.461538460.6583838067.1911.843T0
60SSER55.38461538-0.5324912965.7672.098T0
61KLYS1000.700915065.1742.842T0
62IILE52.30769231-0.6175538033.7361.993T0
63IILE1000.700915063.0192.038C0
64TTHR10.76923077-1.7658976514.9891.891C0
65LLEU96.923076920.6158525535.4322.033H0
66KLYS10.76923077-1.7658976514.331.338H0
67KLYS81.538461540.1905400165.572.168H0
68RARG92.307692310.4882587927.3112.921H1
69WTRP1000.700915066.4642.095H1
70QGLN1000.700915065.081.927C0
71LLEU96.923076920.6158525533.1121.611H0
72AALA96.923076920.6158525534.5531.63H0
73LLEU98.461538460.6583838064.8681.763H0
74SSER10.76923077-1.7658976513.2331.218H0
75KLYS96.923076920.6158525533.2511.606H0
76GGLY96.923076920.6158525534.3341.208H0
77VVAL23.07692308-1.4256476223.7631.384H0
78HHIS10.76923077-1.7658976512.8251.623C1
79FPHE66.15384615-0.234772523.172.642C1
80VVAL55.38461538-0.5324912963.7591.554C0
81CCYS96.923076920.6158525534.7821.557C0
82NASN98.461538460.6583838064.8962.292C0
83LLEU90.769230770.4457275388.4662.322C0
84LLEU1000.700915067.7332.667H0
85LLEU98.461538460.6583838068.9892.904H1
86LLEU96.923076920.6158525535.3312.259H1
87FPHE98.461538460.6583838069.2632.893H0
88VVAL93.846153850.53079004510.32.903H1
89TTHR1000.700915066.3422.113H0
90VVAL13.84615385-1.6808351444.6961.964H0
91YTYR1000.700915068.3412.843H1
92SSER98.461538460.6583838068.5132.401H3
93HHIS1000.700915068.2572.412C1
94LLEU93.846153850.5307900457.2582.296C1
95LLEU1000.700915066.4421.83H2
96LLEU1000.700915065.7262.069H2
97VVAL52.30769231-0.6175538037.0922.055H1
98AALA1000.700915067.4261.899H1
99AALA96.923076920.6158525536.371.859H1
100GGLY93.846153850.5307900457.0052.183H1
101LLEU13.84615385-1.6808351447.2512.67C1
102EGLU1000.700915067.7452.88C1
103AALA86.153846150.3181337778.8543.969C1
104PPRO10.76923077-1.7658976516.3693.346C0
105FPHE1000.700915069.9225.073C1
106LLEU98.461538460.6583838067.1873.696H1
107YTYR96.923076920.6158525535.5513.768H1
108LLEU55.38461538-0.5324912966.5024.096H1
109YTYR96.923076920.6158525537.0864.156H0
110AALA1000.700915065.4442.517H0
111LLEU98.461538460.6583838064.5142.715H1
112VVAL7.692307692-1.8509601585.1292.844T2
113YTYR1000.700915065.0372.63T2
114FPHE52.30769231-0.6175538035.621.879T1
115LLEU1000.700915065.2062.241T2
116QGLN98.461538460.6583838063.5952.293C2
117SSER7.692307692-1.8509601584.2121.379T2
118IILE49.23076923-0.702616315.1351.661T0
119NASN53.84615385-0.5750225493.5971.506T0
120FPHE58.46153846-0.4474287880.941.146T0
121VVAL10.76923077-1.7658976512.3521.369C0
122RARG1000.700915062.2121.392C1
123IILE52.30769231-0.6175538031.971.152C1
124IILE84.615384620.2756025243.7621.539C0
125MMET95.384615380.5733212993.7641.383C0
126RARG1000.700915064.0371.011T0
127LLEU7.692307692-1.8509601582.7491.071T0
128WTRP98.461538460.6583838063.1461.029T0
129LLEU98.461538460.6583838061.9281.435T0
130CCYS1000.700915061.6611.039C0
131WTRP1000.700915061.8921.076C0
132KLYS1000.700915061.6852.173C0
133CCYS1000.700915064.6831.536C0
134RARG32.30769231-1.17046017.8922.439T0
135SSER1000.700915069.41.827T0
136KLYS96.923076920.6158525538.4153.242T0
137NASN1000.700915066.8022.557T0
138PPRO1000.700915067.7962.221C0
139LLEU96.923076920.6158525535.1942.947C1
140LLEU95.384615380.5733212995.4843.065C3
141YTYR96.923076920.6158525537.6493.001C2
142DASP95.384615380.5733212999.9543.873C2
143AALA93.846153850.53079004510.4293.132C1
144NASN96.923076920.6158525538.5782.562C2
145YTYR98.461538460.6583838067.6081.876C2
146FPHE98.461538460.6583838066.1032.742C2
147LLEU9.230769231-1.8084289055.6062.181E2
148CCYS98.461538460.6583838063.591.941C2
149WTRP98.461538460.6583838064.0832.703C1
150HHIS98.461538460.6583838064.2182.194C0
151TTHR98.461538460.6583838064.2021.844C0
152NASN30.76923077-1.2129913542.6161.793C0
153CCYS16.92307692-1.5957726373.1891.593C0
154YTYR87.692307690.3606650313.311.783C1
155DASP98.461538460.6583838065.1181.675C1
156YTYR1000.700915066.8161.785C1
157CCYS1000.700915067.9512.698E1
158IILE1000.700915067.4812.226C0
159PPRO1000.700915067.5944.219C1
160YTYR1000.700915068.1223.523C1
161NASN1000.700915067.4223.141C0
162SSER98.461538460.6583838065.4022.958C0
163VVAL89.230769230.4031962846.7413.221C0
164TTHR1000.700915065.633.129C0
165SSER10.76923077-1.7658976511.7141.855C0
166SSER10.76923077-1.7658976513.2751.47C0
167IILE86.153846150.3181337771.421.974C0
168VVAL1000.700915062.7981.517C0
169IILE26.15384615-1.3405851152.5351.115C0
170TTHR1000.700915063.4011.129C0
171SSER33.84615385-1.1279288465.6531.352C0
172GGLY96.923076920.6158525535.5261.675C0
173DASP1000.700915062.4811.179C0
174GGLY1000.700915063.1631.326C0
175TTHR29.23076923-1.2555226073.0841.477C0
176TTHR18.46153846-1.5532413833.9711.593C0
177SSER7.692307692-1.8509601583.8191.216C0
178PPRO98.461538460.6583838061.4311.171C0
179IILE13.84615385-1.6808351443.3151.61C0
180SSER10.76923077-1.7658976515.191.914C0
181EGLU10.76923077-1.7658976516.3882.901C0
182HHIS7.692307692-1.8509601588.5283.082C0
183DASP96.923076920.6158525537.1192.189C0
184YTYR1000.700915068.2042.167C0
185QGLN1000.700915067.7461.686C1
186IILE1000.7009150611.5212.651C2
187GGLY1000.7009150611.2772.255C2
188GGLY1000.700915067.5582.247C1
189YTYR98.461538460.65838380661.649C3
190TTHR10.76923077-1.7658976517.3721.883C2
191EGLU1000.700915066.922.208C1
192KLYS13.84615385-1.6808351446.1362.839C0
193WTRP69.23076923-0.1497100134.8471.844C0
194EGLU13.84615385-1.6808351443.9022.882C1
195SSER1000.700915063.991.918C2
196GVAL1000.700915063.5482.776C1
197VVAL98.461538460.6583838063.0782.439C0
198KLYS1000.700915062.5082.229C0
199DASP1000.700915062.891.748C0
200CCYS10.76923077-1.7658976512.9091.938C0
201VVAL98.461538460.6583838061.5751.657C0
202VVAL95.384615380.5733212991.71.307C0
203LLEU13.84615385-1.6808351441.31.417C0
204HHIS89.230769230.4031962843.3031.882C0
205SSER10.76923077-1.7658976513.3671.769C1
206YTYR96.923076920.6158525534.1652.244C1
207FPHE96.923076920.6158525534.442.609C0
208TTHR96.923076920.6158525538.3262.25C1
209SSER10.76923077-1.76589765110.1652.674C2
210DASP10.76923077-1.76589765111.8712.446C2
211YTYR89.230769230.4031962848.8752.411C2
212YTYR1000.700915067.3711.824C1
213QGLN1000.700915064.5151.79C0
214LLEU1000.700915064.141.727C0
215YTYR10.76923077-1.7658976514.3542.187C1
216SSER98.461538460.6583838063.8471.745C1
217TTHR1000.700915063.171.258C0
218QGLN1000.700915063.0771.555C0
219LLEU30.76923077-1.2129913543.8431.921C0
220SSER36.92307692-1.0428663393.9081.529C0
221TTHR96.923076920.6158525535.4612.421C0
222DASP93.846153850.5307900455.662.589C1
223TTHR1000.700915064.1122.398C2
224GGLY1000.700915064.1062.184C2
225VVAL12.30769231-1.7233663972.8542.007C1
226EGLU87.692307690.3606650312.5641.553C0
227HHIS10.76923077-1.7658976512.3531.177C0
228VVAL10.76923077-1.7658976513.0841.642C0
229TTHR1000.700915063.8581.684C0
230FPHE1000.700915063.8891.1C0
231FPHE1000.700915063.7971.515C0
232IILE96.923076920.6158525534.2951.565C0
233YTYR30.76923077-1.2129913545.9551.611C0
234NASN75.384615380.0204150024.9311.769C0
235KLYS1000.700915063.9332.482C0
236IILE10.76923077-1.7658976514.6913.271C0
237VVAL96.923076920.6158525539.7665.548C1
238DASP10.76923077-1.7658976519.2935.051C2
239EGLU10.76923077-1.7658976519.3475.869C2
240PPRO75.384615380.0204150028.5135.022C2
241EGLU10.76923077-1.7658976516.4573.993C1
242EGLU13.84615385-1.6808351444.993.183C0
243HHIS32.30769231-1.17046015.2793.158C0
244VVAL1000.700915064.7342.583C0
245QGLN1000.700915065.2051.905C0
246IILE96.923076920.6158525536.3492.242C0
247HHIS1000.700915066.1172.348C0
248TTHR1000.700915066.1262.128C0
249IILE1000.700915068.1172.806C0
250DASP1000.700915069.9052.862C0
251GGLY96.923076920.61585255311.0383.828C1
252SSER96.923076920.61585255311.0215.178C2
253SSER1000.700915069.5814.755C2
254GGLY1000.7009150614.265.997C2
255VVAL1000.7009150612.0755.06C2
256VVAL63.07692308-0.31983502714.1425.156C3
257NASN1000.7009150610.1053.622T2
258PPRO96.923076920.61585255312.9254.643T3
259VVAL10.76923077-1.76589765111.5664.129T2
260MMET95.384615380.5733212998.7522.828T1
261EGLU10.76923077-1.7658976517.1782.903C0
262PPRO98.461538460.6583838066.6962.669C0
263IILE1000.700915065.1873.502C0
264YTYR1000.700915068.7775.055C1
265DASP1000.700915069.1824.978C0
266EGLU98.461538460.65838380610.3145.199C1
267PPRO1000.700915067.7644.874C0
268TTHR1000.700915066.6185.434C1
269TTHR93.846153850.5307900456.7436.437C2
270TTHR1000.700915069.0555.59C2
271TTHR1000.7009150611.286.798C2
272SSER1000.7009150610.8835.081C1
273VVAL1000.7009150610.0045.518C0
274PPRO1000.700915069.8825.637C0
275LLEU1000.7009150610.8296.343C0

2.            I-TASSER server for protein structure and function prediction [Internet]. [cited 2020 Apr 12];Available from: https://zhanglab.ccmb.med.umich.edu/I-TASSER/

8.            Gordon DE, Jang GM, Bouhaddou M, et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. bioRxiv 2020;2020.03.22.002386.

28.         Issa E, Merhi G, Panossian B, Salloum T, Tokajian S. SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions. bioRxiv 2020;2020.03.27.012013.