Methods for detecting antiviral-drug resistant virus

A method for detecting the presence or absence of an antiviral drug-resistant HSV, comprising:

• a. identifying one or more HSV mutation selected from:
• i. a thymidine kinase (TK) mutation selected from 250G>A (HSV-2), 1000>T (HSV-1), 268C>T (HSV-2), 373C>T (HSV-1), 146T>G (HSV-1), 363G>A (HSV-1), 497T>A (HSV-1), 558G>T (HSV-2), 641A>G (HSV-2), 715T>C (HSV-1), 938T>C (HSV-2), 437_438 insA (HSV-1), 169delC (HSV-1), 170delC (HSV-1), 171delC (HSV-1), 172delC (HSV-1), 458delC (HSV-2), 459delC (HSV-2), 460delC (HSV-2), 461delC (HSV-2), 881delC (HSV-1), 882delC (HSV-1), 883delC (HSV-1), 884delC (HSV-1), and 885delC (HSV-1);
• and
• ii. a DNA polymerase (DNA pol) mutation selected from 2405T>G (HSV-1), 2500G>T (HSV-1), 2515A>G (HSV-1), 2892_2893 insT (HSV-1), 2893_2894 insT (HSV-1), 2894_2895 insT (HSV-1), and 2895_2896 insT (HSV-1);
• wherein the presence of said one or more HSV mutation confirms the presence of an antiviral drug-resistant HSV, and wherein the absence of said one or more HSV mutation is indicative of the absence of an antiviral drug-resistant HSV.

A method for detecting the presence or absence of an antiviral drug-resistant HSV, comprising:

• a. identifying the presence or absence of one or more HSV polymorphism in a database comprising:
• i. thymidine kinase (TK) polymorphisms E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• and
• ii. a DNA polymerase (DNA pol) polymorphisms L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• wherein the presence of said one or more HSV polymorphism(s) confirms the presence of an antiviral drug-resistant HSV, and wherein the absence of said one or more HSV polymorphism(s) is indicative of the absence of an antiviral drug-resistant HSV.

A method for detecting the presence or absence of an antiviral drug-resistant HSV, comprising:

• a. identifying one or more HSV polymorphism selected from:
• i. a TK polymorphism selected from E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• and
• ii. a DNA pol polymorphism selected from L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• wherein the presence of said one or more HSV polymorphism confirms the presence of an antiviral drug-resistant HSV, and the absence of said one or more HSV polymorphism is indicative of the absence of an antiviral drug-resistant HSV.

The method according to any one of the preceding claims, further comprising:

• a. identifying one or more HSV-1 TK mutation selected from:
• 110C>T, 205C>A, 1072A>C, 1072A>T, 574G>A, and 766C>T;
• b. identifying one or more HSV-2 TK mutation selected from:
• 373G>A, 639A>C or 639A>T, and 1094T>C;
• c. identifying one or more HSV-1 DNA Pol mutation selected from:
• 64G>A, 160A>G, 248A>C, 361G>A, 415G>A or 415G>C, 716C>T, 1255C>A, 2039A>C, 2042G>A, 2249A>C, 2548G>C, 2732G>A, 2741C>T, 2915C>T, 2954G>A, 2974G>A, 2977C>T, 3137A>C, 3343G>A, 3359A>C, 3505G>A, and 3595C>A;
• and/or
• d. identifying one or more HSV-2 DNA Pol mutation selected from:
• 520G>T, 1339A>C or 1339A>T, 1481T>C, 2141A>G, 2281G>A, 2323C>T, 2325C>G, and 2326G>C;
• wherein the presence of said one or more HSV mutation is indicative of the absence of an antiviral drug-resistant HSV.

The method according to any one of the preceding claims, further comprising:

• a. identifying one or more HSV-1 TK polymorphism selected from:
• A37V, L69M, 1358L, A192T, and R256W;
• b. identifying one or more HSV-2 TK polymorphism selected from:
• A125T, E213D, and L365P;
• c. identifying one or more HSV-1 DNA Pol polymorphism selected from:
• G22R, T54A, D83A, G121S, G139R, S239L, L4191, E680A, R681Q, K750T, E850Q, S911N, S914L, A972V, G985E, E992K, R993C, N1046T, A1115T, E1120A, A1169T, and P1199T;
• and/or
• d. identifying one or more HSV-2 DNA Pol polymorphism selected from:
• D174Y, M447L, M494T, H714R, E761K, R775C, R775W, and E776Q;
• wherein the presence of said one or more HSV polymorphism is indicative of the absence of an antiviral drug-resistant HSV.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. identifying the presence or absence of one or more HSV mutation in a database comprising TK mutations 250G>A (HSV-2), 100C>T (HSV-1), 268C>T (HSV-2), 373C>T (HSV-1), 146T>G (HSV-1), 363G>A (HSV-1), 497T>A (HSV-1), 558G>T (HSV-2), 641A>G (HSV-2), 715T>C (HSV-1), 938T>C (HSV-2), 437_438 insA (HSV-1), 169delC (HSV-1), 170delC (HSV-1), 171delC (HSV-1), 172delC (HSV-1), 458delC (HSV-2), 459delC (HSV-2), 460delC (HSV-2), 461delC (HSV-2), 881delC (HSV-1), 882delC (HSV-1), 883delC (HSV-1), 884delC (HSV-1), and 885delC (HSV-1);
• b. confirming the presence of said one or more HSV mutation(s);
• and
• c. administering to said subject a drug selected from a foscarnet drug, a cidofovir drug and a docosanol drug;
• or other non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. confirming an antiviral drug-resistant HSV comprises a TK mutation selected from 250G>A (HSV-2), 100C>T (HSV-1), 268C>T (HSV-2), 373C>T (HSV-1), 146T>G (HSV-1), 363G>A (HSV-1), 497T>A (HSV-1), 558G>T (HSV-2), 641A>G (HSV-2), 715T>C (HSV-1), 938T>C (HSV-2), 437_438 insA (HSV-1), 169delC (HSV-1), 170delC (HSV-1), 171delC (HSV-1), 172delC (HSV-1), 458delC (HSV-2), 459delC (HSV-2), 460delC (HSV-2), 461delC (HSV-2), 881delC (HSV-1), 882delC (HSV-1), 883delC (HSV-1), 884delC (HSV-1), and 885delC (HSV-1);
• and
• b. administering to said subject a drug selected from a foscarnet drug, a cidofovir drug and a docosanol drug;
• or other non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. identifying the presence or absence of one or more HSV mutation in a database comprising DNA Pol mutations 2405T>G (HSV-1), 2500G>T (HSV-1), 2515A>G (HSV-1), 2892_2893 insT (HSV-1), 2893_2894 insT (HSV-1), 2894_2895 insT (HSV-1), and 2895_2896 insT (HSV-1);
• b. confirming the presence of said one or more HSV mutation(s);
• and
• c. administering to said subject drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. confirming an antiviral drug-resistant HSV comprises a DNA Pol mutation selected from 2405T>G (HSV-1), 2500G>T (HSV-1), 2515A>G (HSV-1), 2892_2893 insT (HSV-1), 2893_2894 insT (HSV-1), 2894_2895 insT (HSV-1), and 2895_2896insT (HSV-1);
• and
• b. administering to said subject drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. identifying the presence or absence of one or more HSV polymorphism in a database comprising TK polymorphisms E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• b. confirming the presence of said one or more HSV polymorphism(s);
• and
• c. administering to said subject a drug selected from a foscarnet drug, a cidofovir drug and a docosanol drug;
• or other non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. confirming an antiviral drug-resistant HSV comprises a TK polymorphism selected from E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• and
• b. administering to said subject a drug selected from a foscarnet drug, a cidofovir drug and a docosanol drug;
• or other non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. identifying the presence or absence of one or more HSV polymorphism in a database comprising DNA Pol polymorphisms L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• b. confirming the presence of said one or more HSV polymorphism(s);
• and
• c. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

A method for treating an infection of an antiviral drug-resistant HSV in a subject, comprising:

• a. confirming an antiviral drug-resistant HSV comprises a DNA Pol polymorphism selected from L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• and
• b. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. identifying the presence or absence of one or more HSV mutation in a database comprising TK mutations 250G>A (HSV-2), 100C>T (HSV-1), 268C>T (HSV-2), 373C>T (HSV-1), 146T>G (HSV-1), 363G>A (HSV-1), 497T>A (HSV-1), 558G>T (HSV-2), 641A>G (HSV-2), 715T>C (HSV-1), 938T>C (HSV-2), 437_438 insA (HSV-1), 169delC (HSV-1), 170delC (HSV-1), 171delC (HSV-1), 172delC (HSV-1), 458delC (HSV-2), 459delC (HSV-2), 460delC (HSV-2), 461delC (HSV-2), 881delC (HSV-1), 882delC (HSV-1), 883delC (HSV-1), 884delC (HSV-1), and 885delC (HSV-1);
• and
• b. confirming the presence of said one or more HSV mutation(s);
• and
• c. administering to said subject a drug selected from foscarnet, cidofovir drug and docosanol;
• or other non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. confirming an antiviral drug-resistant HSV comprises a TK mutation selected from 250G>A (HSV-2), 100C>T (HSV-1), 268C>T (HSV-2), 373C>T (HSV-1), 146T>G (HSV-1), 363G>A (HSV-1), 497T>A (HSV-1), 558G>T (HSV-2), 641A>G (HSV-2), 715T>C (HSV-1), 938T>C (HSV-2), 437_438 insA (HSV-1), 169delC (HSV-1), 170delC (HSV-1), 171delC (HSV-1), 172delC (HSV-1), 458delC (HSV-2), 459delC (HSV-2), 460delC (HSV-2), 461delC (HSV-2), 881delC (HSV-1), 882delC (HSV-1), 883delC (HSV-1), 884delC (HSV-1), and 885delC (HSV-1);
• and
• b. administering to said subject a drug selected from foscarnet, cidofovir drug and docosanol;
• or other non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. identifying the presence or absence of one or more HSV mutation in a database comprising DNA Pol mutations 2405T>G (HSV-1), 2500G>T (HSV-1), 2515A>G (HSV-1), 2892_2893 insT (HSV-1), 2893_2894 insT (HSV-1), 2894_2895 insT (HSV-1), and 2895_2896 insT (HSV-1);
• b. confirming the presence of said one or more HSV mutation(s);
• and
• c. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. confirming an antiviral drug-resistant HSV comprises a DNA Pol mutation selected from 2405T>G (HSV-1), 2500G>T (HSV-1), 2515A>G (HSV-1), 2892_2893 insT (HSV-1), 2893_2894 insT (HSV-1), 2894_2895 insT (HSV-1), and 2895_2896 insT (HSV-1);
• and
• b. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. identifying the presence or absence of one or more HSV polymorphism in a database comprising TK polymorphisms E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• b. confirming the presence said one or more HSV polymorphism(s);
• and
• c. administering to said subject a drug selected from foscarnet, cidofovir drug and docosanol;
• or other non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. confirming an antiviral drug-resistant HSV comprises a TK polymorphism selected from E84K (HSV-2), Q34* (HSV-1), Q90* (HSV-2), Q125* (HSV-1), L49R (HSV-1), M1211 (HSV-1), 1166N (HSV-1), Q186H (HSV-2), H214R (HSV-2), E146fs (HSV-1), D228* (HSV-1), Y239H (HSV-1), L313S (HSV-2), T183* (HSV-1), H58fs (HSV-1), M85* (HSV-1), P154fs (HSV-2), M183* (HSV-2), A294fs (HSV-1), P295fs (HSV-1), and E296fs (HSV-1);
• and
• b. administering to said subject a drug selected from foscarnet, cidofovir drug and docosanol;
• or other non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. identifying the presence or absence of one or more HSV polymorphism in a database comprising DNA Pol polymorphisms L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• b. confirming the presence of said one or more HSV polymorphism(s);
• and
• c. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.

An antiviral drug for use in a method for treating an infection of an antiviral drug-resistant HSV (e.g. HSV-1 and/or HSV-2), wherein said method comprises:

• a. confirming an antiviral drug-resistant HSV comprises a DNA Pol polymorphism selected from L802R (HSV-1), A834S (HSV-1), T839A (HSV-1), F965_I966insF (HSV-1), and 1966* (HSV-1);
• and
• b. administering to said subject a drug selected from a docosanol drug, BAY 54-6322, ASP2151 and BAY 57-1293;
• or other non-foscarnet drug, non-cidofovir drug, non-penciclovir and/or non-acyclovir drug.