Inhibitors of influenza virus replication and uses thereof

1. A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof,

wherein

each of R 1 , R 2 and R 3 is independently H, D, F, Cl, Br, CN, NO 2 , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , OR b , —NR c R d , R b O—C 1-4 alkylene, R d R c N—C 1-4 alkylene, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl; or, R 1 and R 2 , together with the carbon atoms to which they are attached, form a C 3-6 carbocyclic ring, 5- to 6-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 6-membered heteroaromatic ring, and wherein each of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclic ring, 5- to 6-membered heterocyclic ring, C 6-10 aromatic ring and 5- to 6-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, OR b , —NR c R d , C 1-6 alkyl, C 1-6 haloalkyl, R b O—C 1-4 alkylene or R d R c N—C 1-4 alkylene;

R 4 is OR b , —NR c R d , C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 carbocyclyl, C 3-12 carbocyclyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 16-membered heteroaryl or (5- to 16-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 2-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 carbocyclyl, C 3-12 carbocyclyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 16-membered heteroaryl and (5- to 16-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

R 5 is H, D, F, Cl, Br, CN, NO 2 , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , OR b , —NR c R d , R b O—C 1-4 alkylene, R d R c N—C 1-4 alkylene, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 3-12 cycloalkyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 3-12 cycloalkyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

or, R 4 and R 5 , together with the carbon atoms to which they are attached, form a C 3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 10-membered heteroaromatic ring, and wherein each of C 3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C 6-10 aromatic ring and 5- to 10-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

each R′ is independently D, F, Cl, Br, CN, NO 2 , OR b , —NR c R d , R b O—C 1-4 alkylene, R d R c N—C 1-4 alkylene, R a —C(═O)—O—C 1-4 alkylene-O—C 1-4 alkylene, R b O—C(═O)—O—C 1-4 alkylene —O—C 1-4 alkylene, —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1-12 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 1-12 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 3- to 8-membered heterocyclyl, (3- to 8-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO 2 , OR b , —NR c R d , C 1-6 alkyl, C 1-6 haloalkyl, R b O—C 1-4 alkylene or R d R c N—C 1-4 alkylene;

R 6 is H, D or C 1-6 alkyl, and wherein C 1-6 alkyl is optionally substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO 2 or OR b ;

W is C 1-8 alkyl, C 3-12 carbocyclyl or 3- to 12-membered heterocyclyl, and wherein each of C 1-8 alkyl, C 3-12 carbocyclyl and 3- to 12-membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 R w ;

each R w is independently D, F, Cl, Br, CN, NO 2 , ═O, —C(═O)R a , —C(═O)OR b , —C(═O)—O—C 1-4 alkylene-O—C(═O)—OR b , —C(═O)NR c R d , —NR e C(═O)R a , —NR e C(═O)NR c R d , —S(═O) 2 R f , —S(═O) 2 NR e (═O)R a , —S(═O) 2 NR c R d , (R b O) 2 P(═O)—C 0-2 alkylene, OR b , R b O—C 1-2 alkylene, R d R c N—C 1-2 alkylene, C 1-6 alkyl, 5- to 6-membered heteroaryl or 5- to 6-membered heterocyclyl, and wherein each of C 1-6 alkyl, 5- to 6-membered heteroaryl and 5- to 6-membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, N 3 , ═O, NO 2 , OR b , C 1-6 alkyl or C 1-6 haloalkyl;

each R a , R b , R c , R d , R e and R f is independently H, D, hydroxy, C 1-6 haloalkyl, C 1-6 alkyl, n-heptyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, C 3-6 carbocyclyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 1-6 alkyl, n-heptyl, C 1-6 alkoxy, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 carbocyclyl, C 3-6 carbocyclyl-C 1-4 alkylene, 3- to 12-membered heterocyclyl, (3- to 12-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 alkylamino;

or, R c and R d , together with the nitrogen atom to which they are attached, form 3- to 8-membered heterocyclyl or 5- to 8-membered heteroaryl, and wherein each of 3- to 8-membered heterocyclyl and 5- to 8-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 alkylamino.

2. The compound of claim 1 having Formula (II),

wherein A is a C 3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 10-membered heteroaromatic ring; and

q is 0, 1, 2, 3, 4 or 5.

3. The compound of claim 2 , wherein A is a C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 6-membered heteroaromatic ring.

4. The compound of claim 2 , wherein A is a C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, benzene, naphthalene, furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole, benzimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine, thiazole, thiophene, benzothiophene, pyrazine, pyridazine, pyrimidine, indole, purine, quinoline or isoquinoline.

5. The compound of claim 1 , wherein R 4 is OR b , —NR c R d , C 2-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 carbocyclyl, C 3-6 carbocyclyl-C 1-4 alkylene, 5- to 8-membered heterocyclyl, (5- to 8-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 2-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 carbocyclyl, C 3-6 carbocyclyl-C 1-4 alkylene, 5- to 8-membered heterocyclyl, (5- to 8-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

R 5 is H, D, F, Cl, Br, CN, NO 2 , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , OR b , —NR c R d , C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 6-membered heteroaryl or (5- to 6-membered heteroaryl)-C 1-4 alkylene, and wherein each of C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkylene, 5- to 6-membered heterocyclyl, (5- to 6-membered heterocyclyl)-C 1-4 alkylene, C 6-10 aryl, C 6-10 aryl-C 1-4 alkylene, 5- to 6-membered heteroaryl and (5- to 6-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

or, R 4 and R 5 , together with the carbon atoms to which they are attached, form a C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 6-membered heteroaromatic ring, and wherein each of C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, C 6-10 aromatic ring and 5- to 6-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′.

6. The compound of claim 1 , wherein R 4 is OR b , —NR c R d , ethynyl, propinyl, C 3-6 carbocyclyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroisoquinolyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, naphthyl, furyl, benzofuryl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, benzimdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thiadiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolyl, purinyl, quinolyl, isoquinolyl, phenoxathiinyl,

and wherein each of ethynyl, propinyl, C 3-6 carbocyclyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroisoquinolyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, naphthyl, furyl, benzofuryl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, benzimdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thiadiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolyl, purinyl, quinolyl, isoquinolyl, phenoxathiinyl,

is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′;

R 5 is H, D, F, Cl, Br, CN, NO 2 , methyl, ethyl or i-propyl;

or, R 4 and R 5 , together with the carbon atoms to which they are attached, form a C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, benzene, naphthalene, furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole, benzimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine, thiazole, thiophene, benzothiophene, pyrazine, pyridazine, pyrimidine, indole, purine, quinoline or isoquinoline, and wherein each of C 3-6 carbocyclic ring, 3- to 6-membered heterocyclic ring, benzene, naphthalene, furan, benzofuran, pyrrole, pyridine, pyrazole, imidazole, benzimidazole, triazole, tetrazole, oxazole, oxadiazole, 1,3,5-triazine, thiazole, thiophene, benzothiophene, pyrazine, pyridazine, pyrimidine, indole, purine, quinoline and isoquinoline is independently unsubstituted or substituted with 1, 2, 3, 4 or 5 R′.

7. The compound of claim 1 , wherein each of R 1 , R 2 and R 3 is independently H, D, F, Cl, Br, CN, NO 2 , —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , OR b , —NR c R d , methyl, ethyl, n-propyl or i-propyl; or, R 1 and R 2 , together with the carbon atoms to which they are attached, form a C 5-6 carbocyclic ring, 5- to 6-membered heterocyclic ring, benzene ring or 5- to 6-membered heteroaromatic ring, and wherein each of methyl, ethyl, n-propyl, i-propyl, C 5-6 carbocyclic ring, 5- to 6-membered heterocyclic ring, benzene ring and 5- to 6-membered heteroaromatic ring is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, OR b , —NR c R d or C 1-3 haloalkyl.

8. The compound of claim 1 , wherein each R′ is independently D, F, Cl, Br, CN, NO 2 , OR b , —NR c R d , R a —C(═O)—O—C 1-2 alkylene-O—C 1-2 alkylene, R b O—C(═O)—O—C 1-2 alkylene-O—C 1-2 alkylene, —C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , C 1-9 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 5- to 6-membered heterocyclyl, phenyl, pheny-C 1-2 alkylene or 5- to 10-membered heteroaryl, and wherein each of C 1-9 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 5- to 6-membered heterocyclyl, phenyl, pheny-C 1-2 alkylene and 5- to 10-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO 2 , OR b , —NR c R d , methyl, ethyl, n-propyl or i-propyl.

9. The compound of claim 1 , wherein each R′ is independently D, F, Cl, Br, CN, NO 2 , OR b , —NR c R d ,

—C(═O)R a , —C(═O)OR b , —C(═O)NR c R d , methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, trifluoromethyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, cyclopropyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiapyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, phenyl-C 1-2 alkylene, furyl, benzofuranyl, pyrrolyl, pyridinyl, pyrazolyl, imidazolyl, benzimidazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl or pyrimidinyl, and wherein methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, difluoromethyl, monofluoromethyl, 2,2-difluoroethyl, 1,2-difluoroethyl, trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, cyclopropyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiapyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, phenyl-C 1-2 alkylene, furyl, benzofuranyl, pyrrolyl, pyridinyl, pyrazolyl, imidazolyl, benzimidazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, benzothienyl, pyrazinyl, pyridazinyl and pyrimidinyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, NO 2 , OH, —NH 2 , methyl, ethyl, n-propyl or i-propyl.

10. The compound of claim 1 , wherein R 6 is H, D, CF 3 , methyl, ethyl, n-propyl or i-propyl.

11. The compound of claim 1 , wherein W is C 1-6 alkyl, C 5-8 carbocyclyl or 5- to 8-membered heterocyclyl, and wherein each of C 1-6 alkyl, C 5-8 carbocyclyl and 5- to 8-membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 R w .

12. The compound of claim 1 , wherein R w is D, F, Cl, Br, CN, NO 2 , ═O, —C(═O)OCH 3 , —C(═O)OCH 2 CH 3 , —C(═O)OCH 2 CH 2 CH 2 CH 3 , —C(═O)O(CH 2 ) 6 CH 3 , —C(═O)OH,

—C(═O)NR c R d , —NHC(═O)R a , —NHC(═O)NR c R d , —S(═O) 2 R f , —S(═O) 2 NHC(═O)R a , —S(═O) 2 NR c R d , (R b O) 2 P(═O)—C 0-2 alkylene, OR b , methyl, ethyl, n-propyl, i-propyl, furyl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, pyrazinyl, pyridazinyl, pyrimidyl or 5- to 6-membered heterocyclyl, and wherein each of methyl, ethyl, n-propyl, i-propyl, furyl, pyrrolyl, pyridyl, pyrazolyl, imdazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, 1,3,5-triazinyl, thiazolyl, thienyl, pyrazinyl, pyridazinyl, pyrimidyl and 5- to 6-membered heterocyclyl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, Br, CN, N 3 , ═O, NO 2 , —OCH 3 , C 1-3 alkyl or C 1-3 haloalkyl.

13. The compound of claim 1 , wherein each R a , R b , R c , R d , R e and R f is independently H, D, hydroxy, trifluoromethyl, methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, methoxy, ethoxy, C 3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, 5- to 10-membered heteroaryl or (5- to 10-membered heteroaryl)-C 1-4 alkylene, and wherein each of methyl, ethyl, i-propyl, n-propyl, n-butyl, t-butyl, n-pentyl, n-hexyl, n-heptyl, methoxy, ethoxy, C 3-6 carbocyclyl, 5- to 6-membered heterocyclyl, phenyl, 5- to 10-membered heteroaryl and (5- to 10-membered heteroaryl)-C 1-4 alkylene is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH 2 , C 1-3 alkyl, C 1-3 haloalkyl or methoxy;

or, R c and R d , together with the nitrogen atom to which they are attached, form 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl, and wherein each of 5- to 6-membered heterocyclyl and 5- to 6-membered heteroaryl is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from D, F, Cl, CN, OH, NH 2 , C 1-3 alkyl, C 1-3 haloalkyl or methoxy.

14. The compound of claim 1 , wherein W is one of the following sub-formulae:

wherein n is 0, 1, 2, 3 or 4.

15. The compound of claim 1 having Formula (III), (IV), (V), (VI), (VII), (VIII), (IX) or (X):

wherein A is a C 3-12 carbocyclic ring, 3- to 12-membered heterocyclic ring, C 6-10 aromatic ring or 5- to 10-membered heteroaromatic ring; and

q is 0, 1, 2, 3, 4 or 5.

16. The compound of claim 15 having Formula (XI), (XII), (XIII) or (XIV):

17. The compound of claim 1 having one of the following structures:

or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising an effective amount of the compound of claim 1 , and a pharmaceutically acceptable carrier, excipient, vehicle or a combination thereof.

19. The pharmaceutical composition of claim 18 further comprising one or more therapeutic agents, and wherein the therapeutic agent is an anti-influenza virus agent or anti-influenza virus vaccine.

20. The pharmaceutical composition of claim 19 , wherein the therapeutic agent is amantadine, rimantadine, oseltamivir, zanamivir, peramivir, laninamivir, laninamivir octanoate hydrate, favipiravir, umifenovir, ribavirin, stachyflin, 5-[2-(1H-imidazol-5-yl)ethylamino]-5-oxopentanoic acid, fludase, (R)-3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrimidin-4-yl)amino)-4,4-dimethyl pentanoic acid, pimodivir, baloxavir marboxil, an influenza vaccine or a combination thereof.

21. A method of preventing, managing, treating or lessening a disorder or disease caused by a virus infection in a subject, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , wherein the virus infection is influenza virus infection.

22. A method of inhibiting influenza virus RNA polymerase in a subject, comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .

23. A method of preventing, managing, treating or lessening a disorder or disease caused by a virus infection in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 18 , wherein the virus infection is influenza virus infection.

24. A method of inhibiting influenza virus RNA polymerase in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of 18.