Methods of using azide-modified biomolecules, such as fatty acids, carbohydrates and lipids, to treat a plant, an insect or an animal infected with a virus or to inhibit infectivity of a virus, such as the human immunodeficiency virus, are provided. Also provided are methods of labeling a virus, such as human immunodeficiency virus, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. Also, provided are methods of tracking a virus in vivo, with an azide-modified biomolecule, such as a fatty acid, a carbohydrate, or an isoprenoid lipid. The azide-modified biomolecules may be combined with a pharmaceutically acceptable excipient to produce a pharmaceutical composition, optionally containing another anti-viral agent and/or a delivery agent, such as a liposome.

Various embodiments described herein are directed to compounds of formula (I), (II), (III) or (IV) for use as potent inhibitors of HIV integrase and for treatment of patients afflicted with AIDS. A major challenge of human immunodeficiency virus (HIV) chemotherapy continues to be the inevitable selection of resistance by the virus towards known drug regimens. Treating resistant HIV strains calls for novel antivirals with unique structural cores. Some embodiments are directed to compounds featuring a 3-hydroxypyrimidine-2,4-dione-5-carboxamide core that consistently confers low nanomolar potencies against HIV-1 in cell culture. Biochemical testing and molecular modeling results corroborate an antiviral mechanism of action of inhibiting integrase strand transfer (INST). Preliminary testing against raltegravir-resistant HIVs showed marginal cross resistance, suggesting that the chemotypes of the various embodiments described herein could fit an inhibitory profile of second generation INSTIs. ##STR00001##

A method of treating a subject at risk for having an HIV-1 virus infection, by administering to the subject a prophylactically effective amount of a composition comprising a CRISPR-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of proviral DNA of the virus that is unique from the genome of the host cell, cleaving a double strand of the proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease, cleaving a double strand of the proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease, excising an entire HIV-1 proviral genome, and eradicating the HIV-1 proviral DNA from the host cell and preventing HIV-1 retroviral infection.

A method of treating a subject having or at risk for having a virus infection, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus, and completely excising a fragment of greater than 9000-bp of integrated proviral DNA that spanned from its 5- to 3-LTRs. A method of treating a subject having or at risk for having a genetic caused disease, by administering a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs that are complementary to two target sequences spanning from the sequence of the subjects DNA greater than 9000-bp that is chromosomally integrated and causes the genetic caused disease, and excising the chromosomally integrated sequence.

A method of treating a subject at risk for having a virus infection, by administering to the subject a prophylactically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus, and preventing a retroviral infection.

A method of treating a subject having or at risk for having a virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus. A method of treating a subject having or at risk for having a virus infection, by administering to the subject a therapeutically effective amount of a composition comprising a vector encoding a CRISPR-associated endonuclease and at least two guide RNAs, wherein the guide RNAs are complementary to two target sequences spanning from the 5- to 3-LTRs of the sequence in the virus, and causing neither genotoxicity nor off-target editing to the host.

A personalized method of inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus, by determining a nucleic acid sequence of the proviral DNA harbored by a subject, designing two or more different guide RNAs (gRNAs) complementary to the proviral DNA sequences in the subject, treating the subject's host cells with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the proviral DNA, and inactivating the proviral DNA.

A method of preventing transmission of a retrovirus from a mother to her offspring, by treating the mother's host cells with a composition comprising a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the proviral DNA, and preventing transmission of the proviral DNA to the offspring.

A composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including an isolated nucleic acid encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, an isolated nucleic acid sequence encoding a first guide RNA (gRNA) having a first spacer sequence that is complementary to a first target protospacer sequence in a proviral DNA, and an isolated nucleic acid sequence encoding a second gRNA having a second spacer sequence that is complementary to a second target protospacer sequence in the proviral DNA, wherein said first target protospacer sequence and said second target protospacer sequence are situated in a long terminal repeat (LTR) of the proviral DNA. A pharmaceutical composition for use in inactivating a proviral DNA integrated into the genome of a host cell latently infected with a retrovirus.

A pharmaceutical composition for use in inactivating an HIV-1 proviral DNA integrated into the genome of a host cell latently infected with a retrovirus including a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease, and two or more different multiplex guide RNAs (gRNAs), wherein each of the at least two gRNAs is complementary to a different target nucleic acid sequence in a long terminal repeat (LTR) of the HIV-1 proviral DNA, whereby treating the host cell with the composition cleaves a double strand of the HIV-1 proviral DNA at a first target protospacer sequence with the CRISPR-associated endonuclease and cleaves a double strand of the HIV-1 proviral DNA at a second target protospacer sequence with the CRISPR-associated endonuclease and thereby excises an entire HIV-1 proviral genome and eradicates the HIV-1 proviral DNA from the host cell, and a pharmaceutically acceptable carrier.